Open Access

Non‑coding RNAs: Role of miRNAs and lncRNAs in the regulation of autophagy in hepatocellular carcinoma (Review)

  • Authors:
    • Jia Wu
    • Ying Zhu
    • Qingwei Cong
    • Qiumin Xu
  • View Affiliations

  • Published online on: April 20, 2023     https://doi.org/10.3892/or.2023.8550
  • Article Number: 113
  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The term autophagy describes a process that supports nutrient cycling and metabolic adaptation that is accomplished via multistep lysosomal degradation. These activities modulate cell, tissue and internal environment stability, and can also affect the occurrence and development of cancer. Previous studies have mostly described autophagy as having dual effects in cancer, serving to limit tumorigenesis in the early stages of cancer, but promoting tumor progression in certain types of cancer. There have been indications in recent years that microRNAs (miRNAs/miRs) and long non‑coding RNAs (lncRNAs), as types of non‑coding RNAs, play major roles in the occurrence, invasion, development and drug resistance of hepatocellular carcinoma (HCC) and in the migration of HCC cells by governing HCC cell autophagy. Therefore, understanding which miRNAs and lncRNAs play such roles and the relevant molecular mechanisms is critical. The present review highlights the significant functions of miRNAs and lncRNAs in the regulation of autophagy in HCC and the relevant mechanisms, aiming to provide novel insight into HCC therapeutics.

Introduction

Cancer is a prominent cause of morbidity and mortality worldwide, and hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality (1,2). Autophagy is generally understood to be a process that serves to carry cytoplasmic cargo to lysosomes for degradation, which plays a major role in eukaryotic cells and mammalian survival, as well as in cellular homeostasis, development, tumorigenesis and infection (3,4). There are three main types of autophagy: Microautophagy, macroautophagy and chaperone-mediated autophagy (5). Among the three types of autophagy, macroautophagy, generally referred to as ‘autophagy’, is the most critical and most extensively studied form. There is evidence to indicate that autophagy plays a role in inhibiting the growth of tumors, particularly in the liver. In addition to the typical function of autophagy as an inhibitor of tumor development in non-tumor cells and in early-stage tumor development, autophagy also enhances tumor cell survival once the tumor has formed (58) (Fig. 1). Therefore, the inhibition of autophagy has become a novel strategy for anticancer therapeutics (9).

RNAs are transcription products of DNA, and they encompass non-coding RNAs (ncRNAs) and coding RNAs. Coding RNAs include messenger RNAs (mRNAs), which serve as a template for protein biosynthesis (10). ncRNAs are transcripts without protein-coding potential that have multiple biological functions, and they modulate gene expression at multiple levels, affecting processes such as RNA processing, transcription and translation (11). ncRNAs can be categorized into small ncRNAs (sncRNAs), circular RNAs (circRNAs) and lncRNAs (12). The classification of RNAs and their respective roles are summarized in Table I.

Table I.

Classifications and functions of RNAs.

Table I.

Classifications and functions of RNAs.

ClassificationsFunctions(Refs.)
Coding RNAs
  mRNAsActing as template for protein biosynthesis(10)
ncRNAs
  lncRNAsModulating protein localization, mRNA translation and stability in the cytoplasm, taking part in chromatin modification, transcription and post-transcriptional adjustment of gene expression, regulating tumor growth, metastasis and invasion in vitro(1820)
  circRNAsSpecifically binding miRNA to increase the expression level of target genes, regulating transcription, promoting or inhibiting the occurrence of cancer(123125)
  sncRNAs
  snRNAsCatalyzing the splicing of precursor mRNA in the spliceosome, participating in the maturation of mRNA, promoting the development of malignant tumors(126,127)
  snoRNAsRegulating post-transcriptional modification and processing of ribosomal RNA (rRNA) and other RNAs, improving the fidelity and efficiency of translation, promoting or inhibiting tumorigenesis in various types of cancer(126,128130)
  siRNAsRegulating gene silencing and mRNA degradation, inhibiting transcription(131,132)
  miRNAsNegatively regulating gene expression, modulating apoptosis, proliferation, survival and metastasis of cancer cells(13,15)
  piRNAsSilencing transposons, promoting or inhibiting tumorigenesis in tumor tissues(126,133,134)
  Transfer RNAsInvolving in protein translation, promoting the development of cancer(126,135)

[i] lncRNAs, long non-coding RNAs; circRNAs, circular RNAs; sncRNAs, small non-coding RNAs; snRNAs, small nuclear RNAs; snoRNAs, small nucleolar RNAs; siRNAs, small interfering RNAs; miRNAs, microRNAs; piRNAs, PIWI-interacting RNAs.

As a type of sncRNA of ~19–25 nucleotides in length, microRNAs (miRNAs/miRs), have been found to be involved in the negative regulation of gene expression by base pairing with the 3′ untranslated region (UTR) of mRNAs. miRNAs are usually abnormally expressed in tumor cells and can control the apoptosis, proliferation, survival and metastasis of cancer cells (1315). lncRNAs are RNAs >200 nucleotides in length (16), and the majority of lncRNAs are transcribed by RNA Pol II (17). A myriad of functional roles have been attributed to lncRNAs, such as for example, acting in the cytoplasm to modulate protein localization and stability and mRNA translation (18), affecting chromatin modification, the transcription and post-transcriptional processing of transcribed genes (19), and regulating tumor growth, metastasis and invasion in vitro (20). As evidenced by recent discoveries, some miRNAs and lncRNAs have been linked to the occurrence, development, migration, invasion and resistance of HCC cells, due to their association with autophagy, suggesting their potential to modulate autophagy in HCC. For example, miR-26b has been shown to enhance the sensitivity of HCC cells to doxorubicin (Dox) by inhibiting Dox-induced autophagy (21). miR-181a has been found to promote tumor growth and reduce the apoptosis of HCC cells by inhibiting autophagy (22). The lncRNA neighbor of BRCA1 gene 2 (NBR2) suppresses HCC cell proliferation by inhibiting Beclin-1-dependent autophagy (23). miR-30a accelerates the metastasis and recurrence of HCC by promoting autophagy (24). Therefore, miRNAs and lncRNAs play essential roles in the progression of HCC. The present review summarizes the mechanisms and roles of related miRNAs and lncRNAs in regulating autophagy in HCC in an aim to provide insight into their potential role as therapeutic targets for HCC.

miRNAs involved in the regulation of autophagy in HCC

The diverse functions of miRNAs include mediating HCC cell growth, metastasis, autophagy and resistance to drugs, and the association between certain miRNAs and the prognosis of HCC patients is significant. Some miRNAs are abnormally expressed in HCC, and this abnormal expression results in various effects. Some miRNAs involved in regulatory processes and the relevant mechanisms of action are summarized below (Table II). This information will hopefully aid the identification of novel targets for HCC treatment.

Table II.

Role of miRNAs in the regulation of autophagy in HCC.

Table II.

Role of miRNAs in the regulation of autophagy in HCC.

miRNAsExpression level in HCCPathway of action or targetsRegulation of autophagyFunction in HCC(Refs.)
miR-541LowATG2A and RAB1BPromotesPromoting proliferation, migration and invasion(28)
miR-490-3pLowATG7PromotesPromoting proliferation(31)
miR-142-3pLowATG5 and ATG16L1PromotesReducing sensitivity to sorafenib(33)
miR-223LowFOXO3aPromotesReducing sensitivity to adriamycin(39)
miR-375LowATG7PromotesInhibiting apoptosis(42)
miR-26LowULK1PromotesInhibiting apoptosis, increasing resistance to doxorubicin(45)
miR-101LowRAB5A, STMN1 and ATG4DPromotesPromoting resistance to cisplatin(49)
miR-101LowEZH2PromotesPromoting proliferation, inhibiting apoptosis and promoting resistance to chemotherapy drugs(48)
miR-7LowATG5PromotesPromoting invasion and migration(52)
miR-30aLowBeclin 1 and ATG5PromotesPromoting recurrence and migration(24)
miR-559LowPARD3PromotesPromoting proliferation(55)
miR-513b-5pLowPIK3R3PromotesPromoting proliferation(56)
miR-125bLowEVA1APromotesPromoting cell proliferation, invasion and EMT, increasing resistance to oxaliplatin(58)
miR-34aLowBACH1InhibitsPromoting the metastasis and invasion(59)
miR-199a-5pLowATG7PromotesIncreasing resistance to cisplatin(61)
miR-26bLowUSP9X/P53PromotesReducing sensitivity to doxorubicin(21)
miR-1307HighCALR-OSTC endoplasmic reticulum protein folding pathwayInhibitsPromoting proliferation(65)
miR-181aHighATG5InhibitsPromoting proliferation and inhibiting apoptosis(22)
miR-193a-3pHighTGF-β2InhibitsPromoting apoptosis(67)
miR-25HighFBXW7PromotesIncreasing resistance to sorafenib(68)
miR-4790-3pHighZNF225PromotesInhibiting apoptosis(69)

[i] HCC, hepatocellular carcinoma; miR, microRNA; ATG2A, autophagy-related gene 2A; RAB1B, Ras-related protein Rab-1B; ATG, autophagy-related gene; ATG16L1, autophagy-related 16-like 1; ULK1, unc-51 like autophagy activating kinase 1; RAB5A, RAB GTPase 5A; STMN1, stathmin 1; ATG4D, autophagy-related protein 4D; EZH2, enhancer 1 of zeste homolog 2; PIK3R3, phosphoinositide-3-kinase regulatory subunit 3; BACH1, BTB domain and CNC homology 1; USP9X, Ubiquitin-specific protease-9; FBXW7, F-Box and WD repeat domain containing 7; ZNF225, zinc finger protein225.

Low expression of miRNAs in HCC
miR-541

miR-541, a newly identified miRNA cluster, lies in a gene containing a large number of miRNAs (Mirg) within the DLK-DIO3 locus (25). The proliferation, invasion and migration of osteosarcoma and squamous cell lung cancer cells has been shown to be decreased with the increased the expression of miR-541 (26,27). Furthermore, miR-541 limits HCC occurrence and the autophagy of HCC cells by downregulating autophagy-related gene (ATG)2A and Ras-related protein (RAB)1B (28). As previously demonstrated, low levels of miR-541 increase autophagy and promote proliferation, invasion and migration, and a low expression of miR-541 is associated with a poor prognosis of patients with HCC. Similarly, a high expression of miR-541 indicates the superior sensitivity of HCC to sorafenib treatment (28).

miR-490-3p

miR-490-3p is located on chromosome 7q33 in the second intron of CHRM2 and consists of 22 nucleotides. Research has indicated that miR-490-3p can decrease the metastasis and growth of lung adenocarcinoma cells and gastric cancer cells (29,30). In HCC, miR-490-3p can suppress autophagy in HCC cells by targeting ATG7, thus decreasing proliferation and stalling the cell cycle, and an increased miR-490-3p expression indicates a good prognosis (31).

miR-142-3p

miR-142-3p is located on human chromosome 17q22 and is a member of the miR-142 family (32,33). miR-142-3p inhibits the tumorigenesis of colorectal cancer by targeting β-catenin and suppresses the occurrence of breast cancer (34,35). A previous study confirmed that the decreased expression of miR-142-3p accelerated sorafenib-induced HCC cell autophagy through the upregulation of ATG5 and ATG16L1, accordingly reducing HCC cell sensitivity to sorafenib. Conversely, the increased expression of miR-142-3p enhanced the sensitivity of HCC cells to sorafenib (33).

miR-223

The miR-223 gene, positioned on Xq12, is regulated by transcription factors, including NFI-A, PU.1 and C/EBPs. miR-233 is a pivotal factor influencing the evolution and homeostasis of the immune system, as for example, modulating specific inflammatory reactions (36,37). In addition, it can also increase the proliferation of breast cancer cells, induce carcinogenic effects in gastric cancer, and promote metastasis and drug resistance in gastric cancer (38). A low expression of miR-223 has been shown to promote the doxorubicin-induced autophagy of HCC cells by targeting FOXO3a, leading to the reduced sensitivity of HCC cells to doxorubicin. However, the overexpression of miR-223 has been shown to enhance the efficacy of doxorubicin in HCC treatment (39).

miR-375

miR-375 is an originally described β-cell-specific miRNA that has a multifunctional regulatory role in immunity and inflammation (40). Moreover, miR-375 is considered to function as a tumor inhibitor in the majority of cancer types, such as in gastric and colon cancer, and it inhibits cancer occurrence and metastasis (40,41). The overexpression of miR-375 has been found to suppress autophagy under hypoxic conditions by preventing the conversion of LC3I into LC3II in HCC cells, and reducing ATG7 expression, leading to a reduction in HCC cell viability (42).

miR-26

The miR-26 family is a group of widely conserved small RNAs with the same sequence in the seed region. Previous studies have illustrated that the target genes of miR-26 have several roles, including modulating cell metabolism, apoptosis, differentiation, proliferation, metastasis and invasion (43,44). miR-26 knockout facilitates autophagy by augmenting the expression of the autophagy promoter, unc-51 like autophagy activating kinase 1, represses cell apoptosis in vivo, and induces HCC tolerance to Dox (45).

miR-101

miR-101 is located on chromosomes 1 and 9. It serves critical functions in proliferation, drug resistance, angiogenesis, apoptosis, metastasis and invasion in multiple cancer types (46,47). miR-101 inhibits HCC progression by targeting enhancer of Zeste homolog 2 in HCC tissues and sensitizes HCC cells to chemotherapeutic drugs (48). Furthermore, miR-101 overexpression inhibits autophagy by exerting effects on RAB5A, stathmin 1, ATG4D and other targets, and induces the apoptosis of HepG2 cells in cooperation with cisplatin, suggesting that miR-101 enhances HepG2 cell sensitivity to cisplatin. A low miR-101 expression has the opposite effects (48,49).

miR-7

miR-7 is an ancient miRNA (50), that is encoded by three genomic loci (9q21, 19q13 and 15q26) (51). It mainly serves as a tumor inhibitor and regulates diverse signaling pathways, for example, inhibiting cancer cell proliferation, survival and migration, but stimulating apoptosis by downregulating the PI3K and MAPK pathways (50). In HCC tissues, the low expression of miR-7 upregulates ATG5 expression, leading to accelerated autophagy, and the resulting response promotes the metastasis and invasion of HCC cells (52).

miR-30a

As a tumor inhibitor, miR-30a is an intronic class miRNA seated on chromosome 6 (53). miR-30a has been found to modulate numerous biological processes related to apoptosis, proliferation, metastasis, invasion and drug sensitivity (54). miR-30a is related to vascular infiltration, metastatic potential and disease recurrence in HCC, and its decreased expression promotes autophagy by modulating Beclin-1 and ATG5, thereby promoting the metastasis and recurrence of HCC (24).

miR-559

The low expression of miR-559 can inhibit HCC processes. Par-3 family cell polarity regulator (PARD3) regulates cell metastasis and proliferation in a number of cancer types. Research has indicated that miR-559 can suppress the growth of HCC by suppressing PARD3 expression to inhibit autophagy, thus demonstrating that miR-559 has potential as a target for HCC treatment (55).

miR-513b-5p

miR-513b-5p is an miRNA that is downregulated in HCC cells, and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) is an oncogene. miR-513b-5p inhibits PIK3R3 expression by targeting it, thereby inhibiting autophagy during HCC malignant progression. Therefore, miR-513b-5p may be a potential therapeutic target for HCC (56).

miR-125b

miR-125b is located on chromosome 21q21 and is part of the miR-125 family; it plays a crucial role in cancer occurrence and development (57). Research has suggested that miR-125b is expressed in low levels in oxaliplatin-resistant HCC cells, and miR-125b overexpression inhibits invasion, proliferation and epithelial-mesenchymal transition (EMT), indicating that miR-125b may enhance the sensitivity of cells to oxaliplatin. Mechanistically, miR-125b inhibits EMT and autophagy by downregulating Eva-1 homolog A, thereby reducing resistance to oxaliplatin in patients with liver cancer (58).

miR-34a

miR-34a, a member of the miR-34 family, is located on chromosome 1q36.22 (59). Ten-eleven translocation 1, a DNA demethylase, can catalyze miR-34a demethylation, thereby activating miR-34a. miR-34a suppresses BTB domain and CNC homology 1 levels, thus activating the p53 pathway, ultimately promoting autophagy in and repressing metastasis and invasion of HCC cells (59).

miR-199a-5p

miR-199a-5p belongs to the miR-199a family and functions as a tumor inhibitor in lung cancer (60). miR-199a-5p expression has been found to be markedly decreased in patients with HCC receiving cisplatin chemotherapy. Cisplatin-induced miR-199a-5p downregulation activates autophagy by targeting ATG7, thus promoting HCC resistance to cisplatin (61).

miR-26b

miR-26b is encoded in 9p21.3, a vulnerable site in the genome (21). miR-26b expression has been shown to be decreased in HCC tissues treated with Dox. miR-26b promotes p53 degradation by reducing ubiquitin-specific protease-9 expression and inhibiting autophagy induced by Dox, thereby enhancing HCC sensitivity to Dox (21).

High expression of miRNAs in HCC
miR-1307

miR-1307, a gene on human chromosome 10 (62), can regulate ovarian cancer resistance to chemotherapy and increase the proliferation of prostate cancer cells (63,64). miR-1307 suppresses HCC cell autophagy and accelerates the malignant progression of HCC through the Calr-OSTC endoplasmic reticulum protein folding pathway (65).

miR-181a

Research has demonstrated that miR-181a can repress autophagy in a variety of cancer types. In HCC, miR-181a expression is high. Luciferase analysis has suggested that ATG5 is a target of miR-181a. miR-181a can suppress autophagy in HCC cells by targeting ATG5, which reduces HCC cell apoptosis and increases tumor growth (22).

miR-193a-3p

miR-193a-3p is located on chromosome 17 and functions as a tumor suppressor gene in the majority of cancer types (66). In HCC, miR-193a-3p is regulated by mitogen-inducible gene 6 (Mig-6), a tumor inhibitor gene. TGF-β2 is a target of miR-193a-3p. Mig-6 decreases the TGF-β2 level by positively modulating miR-193a-3p and thus promotes apoptosis and suppresses autophagy in HCC (67).

miR-25

miR-25 expression is upregulated in HCC tissues and is associated with the clinical stage, lymph node metastasis and pathological grade. miR-25 promotes HCC resistance to sorafenib by reducing F-box and WD repeat domain containing 7 protein expression to activate autophagy. Therefore, miR-25 may be a novel target for HCC therapy (68).

miR-4790-3p

At present, there are few studies available on miR-4790-3p. As previously demonstrated, in patients with HCC treated with a combination of everolimus and Ku0063794, miR-4790-3p expression is markedly decreased, and the expression of zinc finger protein 225 (ZNF225), which is a target of miR-4790-3p, is significantly increased. The downregulation of miR-4790-3p suppresses autophagy by promoting ZNF225 expression, thereby reducing HCC cell survival (69).

lncRNAs involved in the regulation of autophagy in HCC

Previous studies have demonstrated that lncRNAs are vital for processes related to the occurrence and development of HCC [e.g., autophagy, drug resistance, malignant progression and hypoxia/reoxygenation (H/R) damage in HCC cells] (7073). lncRNAs can also serve as biomarkers for predicting the survival and recurrence rates of various types of cancer. lncRNAs have different expression levels in HCC and thus play differential roles. Below, the mechanisms through which some lncRNAs are modulated in HCC and their mechanisms are summarized, providing insight into the prevention and treatment of HCC (Table III).

Table III.

Role of lncRNAs in the regulation of autophagy in HCC.

Table III.

Role of lncRNAs in the regulation of autophagy in HCC.

miRNAsExpression level in HCCPathway of action or targetsRegulation of autophagyFunction in HCC(Refs.)
MEG3LowPI3K/Akt/mTORPromoteInhibiting apoptosis(75,77)
RP11-295G20.2HighPTENInhibitPromoting proliferation(79)
NEAT1HighmiR-204/ATG3PromoteIncreasing resistance to sorafenib(81)
DCST1-AS1HighAKT/mTOR signaling pathwayInhibitPromoting proliferation and invasion, inhibiting apoptosis(70)
HCG11High miR-26a-5p/ATG12PromotePromoting proliferation and metastasis, inhibiting apoptosis(85)
CCAT1High miR-181a-5p/ATG7PromotePromoting proliferation(87)
MCM3AP-AS1HighmiR-455/EGFRPromotePromoting metastasis(89)
SNHG1HighSLC3A2/Akt pathwayInhibitPromoting resistance to sorafenib(92)
LINC00160HighmiR-132/PIK3R3PromoteInhibiting apoptosis and promoting drug resistance(71)
PVT1HighmiR-365/ATG3PromotePromoting proliferation(97)
HAGLROSHighmiR-5095PromotePromoting proliferation, inhibiting apoptosis(101)
HULCHigh miR-383-5p/VAMP2PromotePromoting proliferation, inhibiting apoptosis and chemotherapy sensitivity to oxaliplatin(103)
HULCHighUSP22/Sirt1PromoteInhibiting chemotherapy sensitivity(104)
SNHG16High miR-23b-3p/EGR1PromoteMaintaining resistance to sorafenib(107)
H19HighPI3K-Akt-mTOR pathwayPromoteInducing hypoxia/reoxygenation (H/R) injury(73)
LINC00665High miR-186-5p/MAP4K3InhibitPromoting proliferation, inhibiting apoptosis(110)
HIF1A-AS1HighHIF-1α/mTORInhibitPromoting proliferation(111)
HNF1A-AS1HighmiR-30b/ATG5PromotePromoting proliferation, inhibiting apoptosis(113)
DANCRHigh miR-222-3p/ATG7PromotePromoting proliferation(115)
ATBHighATG5PromotePromoting proliferation(117)
MALAT1HighmiR-146a/PI3KInhibitPromoting proliferation, inhibiting apoptosis(118)
CCAT2HighmiR-4496/ATG5PromotePromoting migration and invasion(120)
MALAT1HighmiR-216bPromoteIncreasing MDR(119)
NEAT1v1HighGABARAPPromoteIncreasing radiation resistance(82)
BANCRHigh miR-590-5P/OLR1PromoteDecreasing sensitivity to sorafenib(122)
NBR2LowERK/JNKPromotePromoting proliferation(23)

[i] HCC, hepatocellular carcinoma; MEG3, maternally expressed gene 3; NEAT1, nuclear enriched abundant transcript 1; miR, microRNA; ATG, autophagy-related gene; HCG11, HLA complex group 11; CCAT1, colon cancer associated transcript 1; EGFR, epidermal growth factor receptor; SNHG1, small nucleolar RNA host gene 1; LINC00160, long intergenic non-protein coding RNA 00160; PIK3R3, phosphoinositide-3-kinase regulatory subunit 3; PVT1, plasmacytoma variant translocation 1; SNHG16, Small nucleolar RNA host gene 16; HULC, highly upregulated in liver cancer; LINC00665, long intergenic non-protein coding RNA 665; MAP4K3, mitogen activated protein kinase kinase kinase kinase 3; DANCR, differentiation antagonizing non-protein coding RNA; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; CCAT2, colon cancer-associated transcript 2; NEAT1v1, nuclear enriched abundant transcript 1 variant 1; GABARAP, gamma-aminobutyric acid receptor-associated protein; BANCR, BRAF-activated non-protein coding RNA; OLR1, oxidized low-density lipoprotein receptor 1; NBR2, neighbor of BRCA1 gene 2; USP22, ubiquitin-specific peptidase 22; Sirt1, silent information regulator 1; HIF-1α, hypoxia inducible factor 1α; VAMP2, vesicle-associated membrane protein-2.

Low expression of lncRNAs in HCC
Maternally expressed gene 3 (MEG3)

As a novel tumor suppressor, MEG3 is an imprinted gene located on chromosome 14q32. Interleukin enhancer-binding factor 3 (ILF3) is a MEG3 conjugate protein. Compared with normal liver cells, HCC cells have a markedly lower expression of MEG3. Adenosine is a nucleotide metabolite with significant cytotoxicity that can induce apoptosis and reduce cell viability and migration. In addition, adenosine inhibits autophagy in HepG2 cells and stimulates MEG3 expression. The overexpression of MEG3 decreases the expression of ILF3 in HepG2 cells, and the downregulation of ILF3 can also inhibit autophagy by decreasing Beclin-1 expression. In general, the overexpression of MEG3 can activate the PI3K/Akt/mTOR pathway by downregulating ILF3 and inactivating the Beclin-1 signaling pathway to inhibit autophagy, thus increasing the cytotoxic effects against HCC cells (7477).

NBR2

NBR2, a long intergenic ncRNA, is located near the BRCA1 gene on human chromosome 17q21 and affects the biological functions and drug resistance of various types of cancer (78). It has been reported that the higher the expression of NBR2, the lower the malignant degree of HCC cells. The lower expression of lncRNA NBR2 can promote HCC cell proliferation by inducing Beclin 1-dependent autophagy (23). It is thus clear that NBR2 could serve as a therapeutic target for HCC.

High expression of lncRNAs in HCC RP11-295G20.2

RP11-295G20.2, which is 465 nucleotides in length, is primarily located in the cytoplasm with very small coding potential in HCC cells and functions as an oncogene in HCC and other types of cancers (79). RP11-295G20.2 inhibits autophagy to fuel HCC cell proliferation in vitro and in vivo, and is associated with recurrence in patients (79). Phosphatase and tensin homolog (PTEN) is a key tumor suppressor. RP11-295G20.2 and the N-terminus of PTEN can be conjugated to promote the interaction between p62 and PTEN, and this interaction induces lysosomal degradation and changes PTEN expression in HCC cells, ultimately resulting in the transcription of ATGs downstream of the PTEN/Akt/FOXO3a signaling pathway (79).

Nuclear enriched abundant transcript 1 (NEAT1)

NEAT1 is upregulated in several types of human cancer. Accumulating evidence suggests that NEAT1 promotes cell growth, invasion and migration, whereas it inhibits apoptosis (80). The overexpression of NEAT1 facilitates autophagy and increases HCC resistance to sorafenib by modulating miR-204 to increase ATG3 expression (81). NEAT1 variant 1 (NEAT1v1), a variant of NEAT1, participates in maintaining cancer stem cells (CSCs) in HCC. CSCs play a crucial role in drug resistance. Evidence has illustrated that NEAT1v1 promotes autophagy through gamma-aminobutyric acid receptor-associated protein, thereby conferring radioresistance to HCC cells (82).

DCST1-AS1

DCST1-AS1, as a lncRNA, has the capacity to accelerate the migration and invasion of triple-negative breast cancer cells (83). The increased expression of DCST1-AS1 is also associated with a poor prognosis of patients with HCC. Functioning via the Akt/mTOR signaling pathway, DCST1-AS1 not only promotes the proliferation and invasion of HCC cells, but also represses their apoptosis and autophagy (70).

HLA complex group 11 (HCG11)

HCG11 is an HCG gene located on chromosome 6p22.2 upstream of MHC I. HCG11 promotes or inhibits the migration, proliferation, apoptosis and invasion and cell cycle progression of tumor cells (84). HCG11 expression is increased in HCC tissues and cells, and the higher the HCG11 expression is, the poorer the prognosis of HCC patients. HCG11 is required for the metastasis, proliferation and autophagy of HCC cells, and suppresses apoptosis by enhancing ATG12 expression via miR-26a-5p in HCC tissues (85).

Colon cancer-associated transcript 1 (CCAT1)

CCAT1 is located on chromosome 8q24.2 and is 2,628 nucleotides in length. In addition to influencing tumor cell proliferation, migration, proliferation and apoptosis, CCAT1 is related to chemotherapeutic resistance (86). In HCC, CCAT1 functions as a sponge for miR-181A-5p to modulate ATG7 expression and thus promote the autophagy and proliferation of HCC cells (87).

MCM3AP-AS1

MCM3AP-AS1 is located on chromosome 21 and can promote or inhibit tumor progression (88). When the MCM3AP-AS1 gene is knocked down, miR-455 expression is sharply upregulated in HCC cells; furthermore, miR-455 targets epidermal growth factor receptor (EGFR) and modulates autophagy. MCM3AP-AS1 overexpression decreases miR-455 expression, subsequently affecting EGFR expression and increasing autophagy, thus promoting the metastasis of HCC cells (89).

Small nucleolar RNA host gene 1 (SNHG1)

SNHG1, a gene on chromosome 11q12.3, has 11 exons (90). SNHG1 can regulate tumor cell proliferation, apoptosis, invasion and migration, as well as other intracellular functions (91). The overexpression of SNHG1 activates the Akt pathway by regulating solute carrier family 3 member 2, thereby restraining autophagy and increasing HCC resistance to sorafenib (92).

LINC00160

Detection of subcellular localization using fluorescence in situ hybridization has suggested that long intergenic non-protein coding RNA 00160 (LINC00160) is localized in the cytoplasm (71) and can mediate chemotherapeutic drug resistance in breast cancer cells and renal cell carcinoma (93,94). The overexpression of LINC00160 activates autophagy by affecting miR-132 targeting of PIK3R3, and increases the viability and drug resistance but inhibits the apoptosis of HCC cells (71).

Plasmacytoma variant translocation 1 (PVT1)

PVT1 is located in the 8q24 chromosome band (95); it is related to the occurrence and development of cancers and may be a prognostic biomarker (96). PVT1 induces the proliferation and autophagy of HCC cells, as it upregulates ATG3 expression through miR-365 (97).

HAGLROS

HAGLROS is a lncRNA (699 bp) encoding only one transcript that is associated with the malignant progression of gastric, lung and nasopharyngeal cancer (98100). The overexpression of HAGLROS increases autophagy by markedly increasing the total quantity of autolysosomes and Beclin-1, LC3II/LC3I and LC3II levels, and decreasing p62 expression levels. Mechanistically, HAGLROS modulates ATG12 expression in a miR-5095-dependent manner in Huh7 cells, ultimately increasing cell proliferation and autophagy and inhibiting apoptosis (101).

Highly upregulated in liver cancer (HULC)

The HULC gene is located on chromosome 6p24.3 and is ~500 nucleotides in length. HULC overexpression is found in many cancer types and is linked to metastasis, increased tumor size and poor prognosis. (102) HULC functions as a factor regulating HCC cell autophagy, subsequently promoting malignant progression of HCC, and decreased HCC cell sensitivity to oxaliplatin can be induced by increasing LC3II-dependent silent information regulator 1 expression in human HCC (72,103105).

Small nucleolar RNA host gene 16 (SNHG16)

SNHG16, located on 17q25.1, is a member of the lncRNA SNHG family; it contains four exons and has 13 splice variants. SNHG16 plays a major role in cell migration, proliferation and invasion in multiple types of cancer, including lung, prostate and breast cancer (106). The poor prognosis of patients with HCC is associated with the increased expression of SNHG16. The overexpression of SNHG16 inhibits miR-23b-3p expression by upregulating early growth response 1, increasing the viability and autophagy of Hep3B/So cells, and inhibiting apoptosis to maintain resistance to sorafenib (107).

H19

H19, a 2.7-kb gene located near the telomere region of chromosome 11p15.5, is expressed by maternal and paternal cell lines, and tumor formation and tumor cell proliferation and migration are related to H19 (108). H19 is highly expressed in HCC cells (HepG2 and HCCLM3). The function of H19 in eliciting H/R injury to HCC cells is mainly based on the upregulation of autophagy induced by activating the PI3K/Akt/mTOR pathway (73).

LINC00665

Long intergenic non-protein coding RNA 665 (LINC00665), located on chromosome 19q13.12, is dysregulated in various types of cancer and influences the proliferation, apoptosis and metastasis of cancer cells (109). LINC00665 expression is increased in HCC and is negatively associated with overall survival (OS). Patients with higher LINC00665 levels have a shorter OS than those with lower LINC00665 levels. Moreover, the silencing of LINC00665 inhibits tumor growth, and induces autophagy and apoptosis via the miR-186-5p/MAP4K3 axis (110).

HIF1A-AS1

lncRNA HIF1A-AS1, located on the antisense strand of the hypoxia inducible factor 1α (HIF-1α) gene, is highly expressed in HCC and is associated with lymph node metastasis, tumor size, TNM stage and OS. In a previous study, the OS was shorter in the higher HIF1A-ASP1 expression group than in the lower HIF1A-ASP1 expression group. HIF1A-AS1 can promote the progression of HCC by reducing HIF-1α/mTOR-mediated autophagy (111).

HNF1A-AS1

HNF1A-AS1, located on chromosome 12, is considered to be a prognostic and diagnostic marker in multiple types of cancer (112). HNF1A-AS1 is often upregulated in HCC, and a high expression of HNF1A-AS1 is associated with tumor size, poor differentiation, multiple tumors and an advanced TNM stage. HNF1A-AS1 facilitates HCC cell growth and inhibits apoptosis via the induction of Bcl-2 expression by inhibiting miR-30b. ATG5 is targeted by miR-30b, and HNF1A-AS1 can promote autophagy by inhibiting miR-30b targeting by ATG5 (113).

Differentiation antagonizing nonprotein coding RNA (DANCR)

DANCR, located on chromosome 4, is a tumor-associated lncRNA (114). DANCR expression is high in HCC and miR-222-3p expression is low. DANCR increases ATG7-induced autophagy and cell proliferation by inhibiting miR-222-3p. To a certain extent, the higher DANCR expression is, the poorer the prognosis of patients with HCC (115).

ATB

ATB is located on chromosome 14 and affects biological functions in a variety of cancer types (116). In HCC tissues, ATB expression is high, and ATB expression is positively associated with TNM stage, survival rate and tumor size in patients with HCC. ATB promotes autophagy by activating YAP and increasing ATG5 expression, and the overexpression of ATB increases HCC cell proliferation (117). However, whether the effects of ATB on the proliferation of HCC cells are mediated through autophagy remains unclear.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)

MALAT1 can promote the malignant progression of cancers, including HCC. MALAT1 expression is upregulated in HCC. MALAT1 induces PI3K expression by downregulating miR-146a expression, thereby activating downstream Akt and mTOR, and ultimately promoting HCC cell proliferation, but inhibiting autophagy and apoptosis (118). In addition, MALAT1 can be upregulated by HIF-2α, thereby reducing the expression of miR-216b to promote autophagy and increase the multidrug resistance of HCC cells (119).

CCAT2

The locus of CCAT2 is located on chromosome 8q24.21. In HCC tissues, the expression of CCAT2 is markedly increased, and an increased expression of CCAT2 is associated with an advanced stage, as well as with venous infiltration. CCAT2 exerts differential effects in the nucleus and cytoplasm. In the cytoplasm, CCAT2 affects HCC cell invasion and migration by regulating the miR-4496/ATG5 axis. In the nucleus, CCAT2 increases ELAVL1 RNA expression and thus inhibits autophagy, thereby promoting the progression of HCC (120).

BRAF-activated nonprotein coding RNA (BANCR)

BANCR is located between 9q21.11 and q21.12. Although BANCR expression varies, BANCR plays a crucial role in regulating biological functions in various types of cancer (121). BANCR expression in HCC tissues is markedly increased, and its expression can be attenuated by rutin. It has been illustrated that BANCR can downregulate miR-590-5P expression, while miR-590-5P targets oxidized low-density lipoprotein receptor 1 (OLR1) to decrease OLR1 expression. Mechanistically, rutin may inhibit autophagy through the BANCR/miRNA-590-5P/OLR1 axis, thereby attenuating sorafenib resistance in HCC cells (122).

The classification and functions of RNAs are summarized in Table I (123135), and the roles of miRNAs and lncRNAs in autophagy in HCC are summarized in Tables II and IIII.

Mechanisms of miRNAs and lncRNAs in the regulation of autophagy in HCC

Autophagy is a multistep process in which multiple ATGs participate. These ATG proteins take part in various stages of autophagy, including the initiation of phagocytosis, nucleation, elongation, closure of autophagosomes, the fusion of autophagosomes with lysosomes and degradation of decomposition products (5) (Fig. 2).

Some miRNAs and lncRNAs participate in the regulation of autophagy by targeting related mRNAs or signaling pathways and can regulate HCC cell metastasis, proliferation, drug resistance and apoptosis by promoting or inhibiting autophagy. Some miRNAs and lncRNAs modulate autophagy by targeting ATGs to influence the biological functions of HCC cells. For example, miR-26/ULK1 (45) affects the initiation of autophagy. miR-541/ATG2A (28), miR-490-3p (31), miR-375 (42), miR-199a-5p/ATG7 (61), miR-7 (52), miR-181a/ATG5 (22), miR-142-3p/ATG5, ATG16L1 (33) and miR-101/ATG4D (49) affect the prolongation of autophagosomes. miR-30a/Beclin-1 and ATG5 (24) affect the nucleation and prolongation of autophagosomes. Among the lncRNAs, NEAT1/miR-204/ATG3 (81), PVT1/miR-365/ATG3 (97), HCG11/miR-26a-5p/ATG12 (85), CCAT1/miR-181a-5p/ATG7 (87), DANCR/miR-222-3p/ATG7 (115), HNF1A-AS1/miR-30b/ATG5 (113), ATB/ATG5 (117) and CCAT2/miR-4496/ATG5 (120) affect the prolongation of autophagosomes. In conclusion, miRNAs and lncRNAs participate in autophagy regulation in HCC via three different mechanisms: i) miRNAs target mRNAs or regulate signaling pathways to regulate autophagy; ii) lncRNAs target mRNAs or regulate signaling pathways to regulate autophagy; and iii) lncRNAs function as competing endogenous RNAs (ceRNAs) of miRNAs to regulate the expression of miRNAs and thus affect the level of mRNAs, regulating autophagy. It is worth noting that some lncRNAs [DCST1-AS1 (70), HCG11 (85), HAGLROS (101), HULC (104), LINC00160 (71), LINC00665 (110), HNF1A-AS1 (113) and MALAT1 (118)] and miRNAs [miR-541 (28), miR-125b (58), miR-181a (22), miR-26 (45) and miR-101 (48)] can affect various biological functions in HCC while regulating autophagy (Fig. 3).

Figure 3.

Schematic diagram of the role of lncRNAs and miRNAs in autophagy in HCC. miR, microRNA; ATG2A, autophagy-related gene 2A; RAB1B, Ras-related protein Rab-1B; EZH2, enhancer of zeste homolog 2; NBR2, neighbor of BRCA1 gene 2; HIF-1α, hypoxia inducible factor 1α; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; PVT1, plasmacytoma variant translocation 1; DANCR, differentiation antagonizing non-protein coding RNA; HCG11, HLA complex group 11; CCAT1, Colon cancer associated transcript 1; LINC00665, Long intergenic non-protein coding RNA 665; MAP4K3, mitogen activated protein kinase kinase kinase kinase 3; HULC, highly upregulated in liver cancer; VAMP2, vesicle-associated membrane protein-2; USP9X, ubiquitin-specific protease-9; ATG16L1, autophagy-related 16-like 1; RAB5A, RAB GTPase 5A; STMN1, stathmin 1; ATG4D, autophagy-related protein 4D; EZH2, enhancer 1 of zeste homolog 2; USP22, ubiquitin-specific peptidase 22; Sirt1, silent information regulator 1; NEAT1v1, nuclear enriched abundant transcript 1 variant 1; GABARAP, gamma-aminobutyric acid receptor-associated protein; SNHG1, small nucleolar RNA host gene 1; SLC3A2, solute carrier family 3 member 2; MALAT1, metastasis associated lung adenocarcinoma transcript 1; NEAT1, nuclear enriched abundant transcript 1; LINC00160, long intergenic non-protein coding rna 00160; PIK3R3, phosphoinositide-3-kinase regulatory subunit 3; SNHG16, small nucleolar RNA host gene 16; BANCR, BRAF-activated non-protein coding RNA; OLR1, oxidized low-density lipoprotein receptor 1; ZNF225, zinc finger protein225; MEG3, maternally expressed gene 3; BACH1, BTB domain and CNC homology 1; CCAT2, colon cancer-associated transcript 2; EGFR, epidermal growth factor receptor.

Conclusions and future perspectives

HCC is a major cause of cancer-related mortality worldwide. The incidence and mortality rate of HCC have been increasing, and with the survival rate decreasing, it is critical to identify strategies or targets to suppress the tumorigenesis, development, metastasis and invasion of HCC, which will lead to novel methods for the treatment and prognosis of HCC. Autophagy involves the transportation of heterogeneous intracellular materials to lysosomes, and it modulates a number of pathological processes. Autophagy plays differential roles in different stages of HCC. It has been demonstrated that ncRNAs (miRNAs and lncRNAs) play a critical role in regulating HCC cell autophagy. In addition, circRNAs can regulate HCC cell autophagy by regulating miRNA expression. Circ-SPECC1 negatively regulates the expression of miR-33a to regulate autophagy and promote HCC tumorigenesis (136). CircCBFB inhibits miR-424-5p and upregulates ATG14, thereby promoting HCC cell proliferation and autophagy (137). Although the role of other ncRNAs in HCC cell autophagy has not yet been extensively studied, it has been shown that N7 methylguanosine tRNA modification promotes the development of esophageal squamous cell carcinoma through the RPTOR/ULK1/autophagy axis (138). Whether this modification plays a role in HCC has not yet been determined. Additional ncRNAs may play a role in autophagy in HCC, and further studies are warranted.

The majority of the miRNAs and lncRNAs mentioned herein can affect the growth, apoptosis, metastasis and drug resistance of HCC cells by regulating autophagy. However, whether miRNAs such as miR-193a-3p, miR-34a, miR-541 and miR-1307, and lncRNAs such as LINC00665, HNF1A-AS1, DANCR, MALAT1, DCST1-AS1, LINC00160, RP11-295G20.2, HCG11, CCAT1, SNHG1, PVT1 and HAGLROS play a biological role by regulating autophagy in HCC remains to be determined. In terms of mechanisms, lncRNAs and miRNAs can directly target mRNAs or signaling pathways to regulate biological functions in HCC. lncRNAs can also function as ceRNAs of miRNAs, regulating their expression, and thus affecting mRNA expression. Therefore, targeting relevant miRNAs and lncRNAs may enable the modulation of multiple biological functions in HCC, providing a novel direction for HCC treatment. However, challenges blocking clinical applications remain.

It is known that miRNAs regulate autophagy in HCC. Thus, it is necessary to study upstream regulatory factors of miRNAs in the future. In addition to lncRNAs, circRNAs are also critical. However, as each miRNA can have multiple targets, different targets can have diverse effects. Therefore, achieving target specificity will be a challenge.

In addition, miRNA and lncRNA knockout animal models are lacking in previous studies, but are necessary to reveal the functions of miRNAs and lncRNAs. Several possible lncRNA knockout methods have emerged, such as the complete deletion of lncRNA genes, the deletion of lncRNA promoters, and the integration of a premature polyadenylation cassette (139). Whether these methods can be used to generate miRNA knockouts is unknown. Moreover, lncRNAs have low sequence similarity across species; thus, translating data from animal models into humans poses a substantial challenge (140). Finally, the efficacy and safety of clinical applications employing miRNAs and lncRNAs remain to be determined. Further research is required to elucidate these issues.

Acknowledgements

Not applicable.

Funding

The present study was funded by the National Natural Science Foundation of China (grant nos. 81673728 and 82274260).

Availability of data and materials

Not applicable.

Authors' contributions

JW acquired the data and wrote the manuscript. YZ conceived the study. QC and QX contributed to the revisions. All authors have read and approved the final manuscript. Data authentication is not applicable.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Yang JD and Roberts LR: Hepatocellular carcinoma: A global view. Nat Rev Gastroenterol Hepatol. 7:448–458. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Lamb CA, Yoshimori T and Tooze SA: The autophagosome: Origins unknown, biogenesis complex. Nat Rev Mol Cell Biol. 14:759–774. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Levine B and Kroemer G: Biological functions of autophagy genes: A disease perspective. Cell. 176:11–42. 2019. View Article : Google Scholar : PubMed/NCBI

5 

Qian H, Chao X, Williams J, Fulte S, Li T, Yang L and Ding WX: Autophagy in liver diseases: A review. Mol Aspects Med. 82:1009732021. View Article : Google Scholar : PubMed/NCBI

6 

Mizushima N and Komatsu M: Autophagy: Renovation of cells and tissues. Cell. 147:728–741. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Ke PY: Diverse functions of autophagy in liver physiology and liver diseases. Int J Mol Sci. 20:3002019. View Article : Google Scholar : PubMed/NCBI

8 

Yazdani HO, Huang H and Tsung A: Autophagy: Dual response in the development of hepatocellular carcinoma. Cells. 8:912019. View Article : Google Scholar : PubMed/NCBI

9 

Wang Y, Xiong H, Liu D, Hill C, Ertay A, Li J, Zou Y, Miller P, White E, Downward J, et al: Autophagy inhibition specifically promotes epithelial-mesenchymal transition and invasion in RAS-mutated cancer cells. Autophagy. 15:886–899. 2019. View Article : Google Scholar : PubMed/NCBI

10 

Shirokikh NE: Translation complex stabilization on messenger RNA and footprint profiling to study the RNA responses and dynamics of protein biosynthesis in the cells. Crit Rev Biochem Mol Biol. 57:261–304. 2022. View Article : Google Scholar : PubMed/NCBI

11 

Cech TR and Steitz JA: The noncoding RNA revolution-trashing old rules to forge new ones. Cell. 157:77–94. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Bella ED, Koch J and Baerenfaller K: Translation and emerging functions of non-coding RNAs in inflammation and immunity. Allergy. 77:2025–2037. 2022. View Article : Google Scholar : PubMed/NCBI

13 

Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Chang Y, Lin J and Tsung A: Manipulation of autophagy by MIR375 generates antitumor effects in liver cancer. Autophagy. 8:1833–1834. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Iorio MV and Croce CM: MicroRNAs in cancer: Small molecules with a huge impact. J Clin Oncol. 27:5848–5856. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Geisler S and Coller J: RNA in unexpected places: Long non-coding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol. 14:699–712. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Statello L, Guo C, Chen L and Huarte M: Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol. 22:96–118. 2021. View Article : Google Scholar : PubMed/NCBI

18 

Mercer TR and Mattick JS: Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol. 20:300–307. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Mercer TR, Dinger ME and Mattick JS: Long non-coding RNAs: Insights into functions. Nat Rev Genet. 10:155–159. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Dhamija S and Diederichs S: From junk to master regulators of invasion: lncRNA functions in migration, EMT and metastasis. Int J Cancer. 139:269–280. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Chen E, Li E, Liu H, Zhou Y, Wen L, Wang J, Wang Y, Ye L and Liang T: miR-26b enhances the sensitivity of hepatocellular carcinoma to doxorubicin via USP9X-dependent degradation of p53 and regulation of autophagy. Int J Biol Sci. 17:781–795. 2021. View Article : Google Scholar : PubMed/NCBI

22 

Yang J, He Y, Zhai N, Ding S, Li J and Peng Z: MicroRNA-181a inhibits autophagy by targeting Atg5 in hepatocellular carcinoma. Front Biosci (Landmark Ed). 23:388–396. 2018. View Article : Google Scholar : PubMed/NCBI

23 

Sheng JQ, Wang MR, Fang D, Liu L, Huang WJ, Tian DA, He XX and Li PY: LncRNA NBR2 inhibits tumorigenesis by regulating autophagy in hepatocellular carcinoma. Biomed Pharmacother. 133:1110232021. View Article : Google Scholar : PubMed/NCBI

24 

Fu XT, Shi YH, Zhou J, Peng YF, Liu WR, Shi GM, Gao Q, Wang XY, Song K, Fan J and Ding ZB: MicroRNA-30a suppresses autophagy-mediated anoikis resistance and metastasis in hepatocellular carcinoma. Cancer Lett. 412:108–117. 2018. View Article : Google Scholar : PubMed/NCBI

25 

Martins M, Galfrè S, Terrigno M, Pandolfini L, Appolloni I, Dunville K, Marranci A, Rizzo M, Mercatanti A, Poliseno L, et al: A eutherian-specific microRNA controls the translation of Satb2 in a model of cortical differentiation. Stem Cell Reports. 16:1496–1509. 2021. View Article : Google Scholar : PubMed/NCBI

26 

Liu C and Yi X: miR-541 serves as a prognostic biomarker of osteosarcoma and its regulatory effect on tumor cell proliferation, migration and invasion by targeting TGIF2. Diagn Pathol. 15:962020. View Article : Google Scholar : PubMed/NCBI

27 

Xu L, Du B, Lu QJ, Fan XW, Tang K, Yang L and Liao WL: miR-541 suppresses proliferation and invasion of squamous cell lung carcinoma cell lines via directly targeting high-mobility group AT-hook 2. Cancer Med. 7:2581–2591. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Xu WP, Liu JP, Feng JF, Zhu CP, Yang Y, Zhou WP, Ding J, Huang CK, Cui YL, Ding CH, et al: miR-541 potentiates the response of human hepatocellular carcinoma to sorafenib treatment by inhibiting autophagy. Gut. 69:1309–1321. 2020. View Article : Google Scholar : PubMed/NCBI

29 

Li Z, Jiang D and Yang S: MiR-490-3p inhibits the malignant progression of lung adenocarcinoma. Cancer Manag Res. 12:10975–10984. 2020. View Article : Google Scholar : PubMed/NCBI

30 

Shen J, Xiao Z, Wu WKK, Wang MH, To KF, Chen Y, Yang W, Li MSM, Shin VY, Tong JH, et al: Epigenetic silencing of miR-490-3p reactivates the chromatin remodeler SMARCD1 to promote Helicobacter pylori-induced gastric carcinogenesis. Cancer Res. 75:754–765. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Ou Y, He J and Liu Y: MiR-490-3p inhibits autophagy via targeting ATG7 in hepatocellular carcinoma. IUBMB Life. 70:468–478. 2018. View Article : Google Scholar : PubMed/NCBI

32 

Fernández C, Bellosillo B, Ferraro M, Seoane A, Sánchez-González B, Pairet S, Pons A, Barranco L, Vela MC, Gimeno E, et al: MicroRNAs 142-3p, miR-155 and miR-203 are deregulated in gastric MALT lymphomas compared to chronic gastritis. Cancer Genomics Proteomics. 14:75–82. 2017. View Article : Google Scholar : PubMed/NCBI

33 

Zhang K, Chen J, Zhou H, Chen Y, Zhi Y, Zhang B, Chen L, Chu X, Wang R and Zhang C: PU.1/microRNA-142-3p targets ATG5/ATG16L1 to inactivate autophagy and sensitize hepatocellular carcinoma cells to sorafenib. Cell Death Dis. 9:3122018. View Article : Google Scholar : PubMed/NCBI

34 

Liu P, Cao F, Sui J, Hong Y, Liu Q, Gao X, Gong H, Hao L, Lou Z and Zhang W: MicroRNA-142-3p inhibits tumorigenesis of colorectal cancer via suppressing the activation of Wnt Signaling by directly targeting to β-catenin. Front Oncol. 10:5529442021. View Article : Google Scholar : PubMed/NCBI

35 

Mansoori B, Duijf PHG, Mohammadi A, Safarzadeh E, Ditzel HJ, Gjerstorff MF, Cho WC and Baradaran B: MiR-142-3p targets HMGA2 and suppresses breast cancer malignancy. Life Sci. 276:1194312021. View Article : Google Scholar : PubMed/NCBI

36 

Rodriguez AE, Hernández JÁ, Benito R, Gutiérrez NC, García JL, Hernández-Sánchez M, Risueño A, Sarasquete ME, Fermiñán E, Fisac R, et al: Molecular characterization of chronic lymphocytic leukemia patients with a high number of losses in 13q14. PLoS One. 7:e484852012. View Article : Google Scholar : PubMed/NCBI

37 

Yuan S, Wu Q, Wang Z, Che Y, Zheng S, Chen Y, Zhong X and Shi F: miR-223: An immune regulator in infectious disorders. Front Immunol. 12:7818152021. View Article : Google Scholar : PubMed/NCBI

38 

Favero A, Segatto I, Perin T and Belletti B: The many facets of miR-223 in cancer: Oncosuppressor, oncogenic driver, therapeutic target, and biomarker of response. Wiley Interdiscip Rev RNA. 12:e16592021. View Article : Google Scholar : PubMed/NCBI

39 

Zhou Y, Chen E, Tang Y, Mao J, Shen J, Zheng X, Xie S, Zhang S, Wu Y, Liu H, et al: miR-223 overexpression inhibits doxorubicin-induced autophagy by targeting FOXO3a and reverses chemoresistance in hepatocellular carcinoma cells. Cell Death Dis. 10:8432019. View Article : Google Scholar : PubMed/NCBI

40 

Liu Y, Wang Q, Wen J, Wu Y and Man C: MiR-375: A novel multifunctional regulator. Life Sci. 275:1193232021. View Article : Google Scholar : PubMed/NCBI

41 

Wei J, Lu Y, Wang R, Xu X, Liu Q, He S, Pan H, Liu X, Yuan B, Ding Y and Zhang J: MicroRNA-375: Potential cancer suppressor and therapeutic drug. Biosci Rep. 41:BSR202114942021. View Article : Google Scholar : PubMed/NCBI

42 

Chang Y, Yan W, He X, Zhang L, Li C, Huang H, Nace G, Geller DA, Lin J and Tsung A: miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions. Gastroenterology. 143:177–187.e8. 2012. View Article : Google Scholar : PubMed/NCBI

43 

Li C, Li Y, Lu Y, Niu Z, Zhao H, Peng Y and Li M: miR-26 family and its target genes in tumorigenesis and development. Crit Rev Oncol Hematol. 157:1031242021. View Article : Google Scholar : PubMed/NCBI

44 

Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M and Croce CM: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:2999–3004. 2004. View Article : Google Scholar : PubMed/NCBI

45 

Jin F, Wang Y, Li M, Zhu Y, Liang H, Wang C, Wang F, Zhang CY, Zen K and Li L: MiR-26 enhances chemosensitivity and promotes apoptosis of hepatocellular carcinoma cells through inhibiting autophagy. Cell Death Dis. 8:e25402017. View Article : Google Scholar : PubMed/NCBI

46 

Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M and Dreyfuss G: miRNPs: A novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev. 16:720–728. 2002. View Article : Google Scholar : PubMed/NCBI

47 

Wang CZ, Deng F, Li H, Wang DD, Zhang W, Ding L and Tang JH: MiR-101: A potential therapeutic target of cancers. Am J Transl Res. 10:3310–3321. 2018.PubMed/NCBI

48 

Xu L, Beckebaum S, Iacob S, Wu G, Kaiser GM, Radtke A, Liu C, Kabar I, Schmidt HH, Zhang X, et al: MicroRNA-101 inhibits human hepatocellular carcinoma progression through EZH2 downregulation and increased cytostatic drug sensitivity. J Hepatol. 60:590–598. 2014. View Article : Google Scholar : PubMed/NCBI

49 

Xu Y, An Y, Wang Y, Zhang C, Zhang H, Huang C, Jiang H, Wang X and Li X: miR-101 inhibits autophagy and enhances cisplatin-induced apoptosis in hepatocellular carcinoma cells. Oncol Rep. 29:2019–2024. 2013. View Article : Google Scholar : PubMed/NCBI

50 

Korać P, Antica M and Matulić M: MiR-7 in cancer development. Biomedicines. 9:3252021. View Article : Google Scholar : PubMed/NCBI

51 

Zhao J, Tao Y, Zhou Y, Qin N, Chen C, Tian D and Xu L: MicroRNA-7: A promising new target in cancer therapy. Cancer Cell Int. 15:1032015. View Article : Google Scholar : PubMed/NCBI

52 

Yuan J, Li Y, Liao J, Liu M, Zhu L and Liao K: MicroRNA-7 inhibits hepatocellular carcinoma cell invasion and metastasis by regulating Atg5-mediated autophagy. Transl Cancer Res. 9:3965–3972. 2020. View Article : Google Scholar : PubMed/NCBI

53 

Rodriguez A, Griffiths-Jones S, Ashurst JL and Bradley A: Identification of mammalian microRNA host genes and transcription units. Genome Res. 14:1902–1910. 2004. View Article : Google Scholar : PubMed/NCBI

54 

Jiang LH, Zhang HD and Tang JH: MiR-30a: A novel biomarker and potential therapeutic target for cancer. J Oncol. 2018:51678292018. View Article : Google Scholar : PubMed/NCBI

55 

Wang C, Li C and Hao R: miR-559 inhibits proliferation, autophagy, and angiogenesis of hepatocellular carcinoma cells by targeting PARD3. Mediators Inflamm. 2022:31214922022. View Article : Google Scholar : PubMed/NCBI

56 

Jin W, Liang Y, Li S, Lin G, Liang H, Zhang Z, Zhang W and Nie R: MiR-513b-5p represses autophagy during the malignant progression of hepatocellular carcinoma by targeting PIK3R3. Aging (Albany NY). 13:16072–16087. 2021. View Article : Google Scholar : PubMed/NCBI

57 

Wang Y, Tan J, Wang L, Pei G, Cheng H, Zhang Q, Wang S, He C, Fu C and Wei Q: MiR-125 family in cardiovascular and cerebrovascular diseases. Front Cell Dev Biol. 9:7990492021. View Article : Google Scholar : PubMed/NCBI

58 

Ren WW, Li DD, Chen X, Li XL, He YP, Guo LH, Liu LN, Sun LP and Zhang XP: MicroRNA-125b reverses oxaliplatin resistance in hepatocellular carcinoma by negatively regulating EVA1A mediated autophagy. Cell Death Dis. 9:5472018. View Article : Google Scholar : PubMed/NCBI

59 

Sun X, Zhu H, Cao R, Zhang J and Wang X: BACH1 is transcriptionally inhibited by TET1 in hepatocellular carcinoma in a microRNA-34a-dependent manner to regulate autophagy and inflammation. Pharmacol Res. 169:1056112021. View Article : Google Scholar : PubMed/NCBI

60 

Meng W, Li Y, Chai B, Liu X and Ma Z: miR-199a: A tumor suppressor with noncoding RNA network and therapeutic candidate in lung cancer. Int J Mol Sci. 23:85182022. View Article : Google Scholar : PubMed/NCBI

61 

Xu N, Zhang J, Shen C, Luo Y, Xia L, Xue F and Xia Q: Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. Biochem Biophys Res Commun. 423:826–831. 2012. View Article : Google Scholar : PubMed/NCBI

62 

Liu Y, Gu X and Liu Y: The effect of dexmedetomidine on biological behavior of osteosarcoma cells through miR-1307 expression. Am J Transl Res. 13:4876–4883. 2021.PubMed/NCBI

63 

Zhou Y, Wang M, Shuang T, Liu Y, Zhang Y and Shi C: MiR-1307 influences the chemotherapeutic sensitivity in ovarian cancer cells through the regulation of the CIC transcriptional repressor. Pathol Res Pract. 215:1526062019. View Article : Google Scholar : PubMed/NCBI

64 

Qiu X and Dou Y: miR-1307 promotes the proliferation of prostate cancer by targeting FOXO3A. Biomed Pharmacother. 88:430–435. 2017. View Article : Google Scholar : PubMed/NCBI

65 

Xie S, Jiang X, Qin R, Song S, Lu Y, Wang L, Chen Y and Lu D: miR-1307 promotes hepatocarcinogenesis by CALR-OSTC-endoplasmic reticulum protein folding pathway. iScience. 24:1032712021. View Article : Google Scholar : PubMed/NCBI

66 

Khordadmehr M, Shahbazi R, Sadreddini S and Baradaran B: miR-193: A new weapon against cancer. J Cell Physiol. 234:16861–16872. 2019. View Article : Google Scholar : PubMed/NCBI

67 

Qu L, Tian Y, Hong D, Wang F and Li Z: Mig-6 inhibits autophagy in HCC cell lines by modulating miR-193a-3p. Int J Med Sci. 19:338–351. 2022. View Article : Google Scholar : PubMed/NCBI

68 

Feng X, Zou B, Nan T, Zheng X, Zheng L, Lan J, Chen W and Yu J: MiR-25 enhances autophagy and promotes sorafenib resistance of hepatocellular carcinoma via targeting FBXW7. Int J Med Sci. 19:257–266. 2022. View Article : Google Scholar : PubMed/NCBI

69 

Choi HJ, Park JH, Kim OH, Kim KH, Hong HE, Seo H and Kim SJ: Combining everolimus and Ku0063794 promotes apoptosis of hepatocellular carcinoma cells via reduced autophagy resulting from diminished expression of miR-4790-3p. Int J Mol Sci. 22:28592021. View Article : Google Scholar : PubMed/NCBI

70 

Li J, Zhai D, Huang Q, Chen HL, Zhang Z and Tan QF: LncRNA DCST1-AS1 accelerates the proliferation, metastasis and autophagy of hepatocellular carcinoma cell by AKT/mTOR signaling pathways. Eur Rev Med Pharmacol Sci. 23:6091–6104. 2019.PubMed/NCBI

71 

Zhang W, Liu Y, Fu Y, Han W, Xu H, Wen L, Deng Y and Liu K: Long non-coding RNA LINC00160 functions as a decoy of microRNA-132 to mediate autophagy and drug resistance in hepatocellular carcinoma via inhibition of PIK3R3. Cancer Lett. 478:22–33. 2020. View Article : Google Scholar : PubMed/NCBI

72 

Xin X, Wu M, Meng Q, Wang C, Lu Y, Yang Y, Li X, Zheng Q, Pu H, Gui X, et al: Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a. Mol Cancer. 17:942018. View Article : Google Scholar : PubMed/NCBI

73 

Cui C, Li Z and Wu D: The long non-coding RNA H19 induces hypoxia/reoxygenation injury by up-regulating autophagy in the hepatoma carcinoma cells. Biol Res. 52:322019. View Article : Google Scholar : PubMed/NCBI

74 

Zhou Y, Zhang X and Klibanski A: MEG3 noncoding RNA: A tumor suppressor. J Mol Endocrinol. 48:R45–R53. 2012. View Article : Google Scholar : PubMed/NCBI

75 

Braconi C, Kogure T, Valeri N, Huang N, Nuovo G, Costinean S, Negrini M, Miotto E, Croce CM and Patel T: microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. Oncogene. 30:4750–4756. 2011. View Article : Google Scholar : PubMed/NCBI

76 

Yu S, Hou D, Chen P, Zhang Q, Lv B, Ma Y, Liu F, Liu H, Song EJ, Yang D and Liu J: Adenosine induces apoptosis through TNFR1/RIPK1/P38 axis in colon cancer cells. Biochem Biophys Res Commun. 460:759–765. 2015. View Article : Google Scholar : PubMed/NCBI

77 

Pu Z, Wu L, Guo Y, Li G, Xiang M, Liu L, Zhan H, Zhou X and Tan H: LncRNA MEG3 contributes to adenosine-induced cytotoxicity in hepatoma HepG2 cells by downregulated ILF3 and autophagy inhibition via regulation PI3K-AKT-mTOR and beclin-1 signaling pathway. J Cell Biochem. 120:18172–18185. 2019. View Article : Google Scholar : PubMed/NCBI

78 

Wang T, Li Z, Yan L, Yan F, Shen H and Tian X: Long non-coding RNA neighbor of BRCA1 gene 2: A crucial regulator in cancer biology. Front Oncol. 11:7835262021. View Article : Google Scholar : PubMed/NCBI

79 

Liang L, Huan L, Wang J, Wu Y, Huang S and He X: LncRNA RP11-295G20.2 regulates hepatocellular carcinoma cell growth and autophagy by targeting PTEN to lysosomal degradation. Cell Discov. 7:1182021. View Article : Google Scholar : PubMed/NCBI

80 

Li K, Yao T, Zhang Y, Li W and Wang Z: NEAT1 as a competing endogenous RNA in tumorigenesis of various cancers: Role, mechanism and therapeutic potential. Int J Biol Sci. 17:3428–3440. 2021. View Article : Google Scholar : PubMed/NCBI

81 

Li X, Zhou Y, Yang L, Ma Y, Peng X, Yang S, Li H and Liu J: LncRNA NEAT1 promotes autophagy via regulating miR-204/ATG3 and enhanced cell resistance to sorafenib in hepatocellular carcinoma. J Cell Physiol. 235:3402–3413. 2020. View Article : Google Scholar : PubMed/NCBI

82 

Sakaguchi H, Tsuchiya H, Kitagawa Y, Tanino T, Yoshida K, Uchida N and Shiota G: NEAT1 confers radioresistance to hepatocellular carcinoma cells by inducing autophagy through GABARAP. Int J Mol Sci. 23:7112022. View Article : Google Scholar : PubMed/NCBI

83 

Tang L, Chen Y, Chen H, Jiang P, Yan L, Mo D, Tang X and Yan F: DCST1-AS1 promotes TGF-β-induced epithelial-mesenchymal transition and enhances chemoresistance in triple-negative breast cancer cells via ANXA1. Front Oncol. 10:2802020. View Article : Google Scholar : PubMed/NCBI

84 

Yuan X, Zhao Q, Zhang Y and Xue M: The role and mechanism of HLA complex group 11 in cancer. Biomed Pharmacother. 143:1122102021. View Article : Google Scholar : PubMed/NCBI

85 

Li M, Zhang Y and Ma L: LncRNA HCG11 accelerates the progression of hepatocellular carcinoma via miR-26a-5p/ATG12 axis. Eur Rev Med Pharmacol Sci. 23:10708–10720. 2019.PubMed/NCBI

86 

Liu Z, Chen Q and Hann SS: The functions and oncogenic roles of CCAT1 in human cancer. Biomed Pharmacother. 115:1089432019. View Article : Google Scholar : PubMed/NCBI

87 

Guo J, Ma Y, Peng X, Jin H and Liu J: LncRNA CCAT1 promotes autophagy via regulating ATG7 by sponging miR-181 in hepatocellular carcinoma. J Cell Biochem. 120:17975–17983. 2019. View Article : Google Scholar : PubMed/NCBI

88 

Yu X, Zheng Q, Zhang Q, Zhang S, He Y and Guo W: MCM3AP-AS1: An indispensable cancer-related LncRNA. Front Cell Dev Biol. 9:7527182021. View Article : Google Scholar : PubMed/NCBI

89 

Zhang H, Luo C and Zhang G: LncRNA MCM3AP-AS1 regulates epidermal growth factor receptor and autophagy to promote hepatocellular carcinoma metastasis by interacting with miR-455. DNA Cell Biol. 38:857–864. 2019. View Article : Google Scholar : PubMed/NCBI

90 

Zhang M, Wang W, Li T, Yu X, Zhu Y, Ding F, Li D and Yang T: Long noncoding RNA SNHG1 predicts a poor prognosis and promotes hepatocellular carcinoma tumorigenesis. Biomed Pharmacother. 80:73–79. 2016. View Article : Google Scholar : PubMed/NCBI

91 

Thin KZ, Tu JC and Raveendran S: Long non-coding SNHG1 in cancer. Clin Chim Acta. 494:38–47. 2019. View Article : Google Scholar : PubMed/NCBI

92 

Li W, Dong X, He C, Tan G, Li Z, Zhai B, Feng J, Jiang X, Liu C, Jiang H and Sun X: LncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and is positively regulated by miR-21 in hepatocellular carcinoma cells. J Exp Clin Cancer Res. 38:1832019. View Article : Google Scholar : PubMed/NCBI

93 

Wu H, Gu J, Zhou D, Cheng W, Wang Y, Wang Q and Wang X: LINC00160 mediated paclitaxel- and doxorubicin-resistance in breast cancer cells by regulating TFF3 via transcription factor C/EBPβ. J Cell Mol Med. 24:8589–8602. 2020. View Article : Google Scholar : PubMed/NCBI

94 

Cheng G, Liu Y, Liu L, Ruan H, Cao Q, Song Z, Bao L, Xu T, Xiong Z, Liu J, et al: LINC00160 mediates sunitinib resistance in renal cell carcinoma via SAA1 that is implicated in STAT3 activation and compound transportation. Aging (Albany NY). 12:17459–17479. 2020. View Article : Google Scholar : PubMed/NCBI

95 

Huppi K, Pitt JJ, Wahlberg BM and Caplen NJ: The 8q24 gene desert: An oasis of non-coding transcriptional activity. Front Genet. 3:692012. View Article : Google Scholar : PubMed/NCBI

96 

Traversa D, Simonetti G, Tolomeo D, Visci G, Macchia G, Ghetti M, Martinelli G, Kristensen LS and Storlazzi CT: Unravelling similarities and differences in the role of circular and linear PVT1 in cancer and human disease. Br J Cancer. 126:835–850. 2022. View Article : Google Scholar : PubMed/NCBI

97 

Yang L, Peng X, Jin H and Liu J: Long non-coding RNA PVT1 promotes autophagy as ceRNA to target ATG3 by sponging microRNA-365 in hepatocellular carcinoma. Gene. 697:94–102. 2019. View Article : Google Scholar : PubMed/NCBI

98 

Zhang W, Zhang Y and Xi S: Upregulation of lncRNA HAGLROS enhances the development of nasopharyngeal carcinoma via modulating miR-100/ATG14 axis-mediated PI3K/AKT/mTOR signals. Artif Cells Nanomed Biotechnol. 47:3043–3052. 2019. View Article : Google Scholar : PubMed/NCBI

99 

Chen JF, Wu P, Xia R, Yang J, Huo XY, Gu DY, Tang CJ, De W and Yang F: STAT3-induced lncRNA HAGLROS overexpression contributes to the malignant progression of gastric cancer cells via mTOR signal-mediated inhibition of autophagy. Mol Cancer. 17:62018. View Article : Google Scholar : PubMed/NCBI

100 

Wang WL, Yu DJ and Zhong M: LncRNA HAGLROS accelerates the progression of lung carcinoma via sponging microRNA-152. Eur Rev Med Pharmacol Sci. 23:6531–6538. 2019.PubMed/NCBI

101 

Wei H, Hu J, Pu J, Tang Q, Li W, Ma R, Xu Z, Tan C, Yao T, Wu X, et al: Long noncoding RNA HAGLROS promotes cell proliferation, inhibits apoptosis and enhances autophagy via regulating miR-5095/ATG12 axis in hepatocellular carcinoma cells. Int Immunopharmacol. 73:72–80. 2019. View Article : Google Scholar : PubMed/NCBI

102 

Yu X, Zheng H, Chan MTV and Wu WKK: HULC: An oncogenic long non-coding RNA in human cancer. J Cell Mol Med. 21:410–417. 2017. View Article : Google Scholar : PubMed/NCBI

103 

Li P, Li Y and Ma L: Long noncoding RNA highly upregulated in liver cancer promotes the progression of hepatocellular carcinoma and attenuates the chemosensitivity of oxaliplatin by regulating miR-383-5p/vesicle-associated membrane protein-2 axis. Pharmacol Res Perspect. 9:e008152021. View Article : Google Scholar : PubMed/NCBI

104 

Xiong H, Ni Z, He J, Jiang S, Li X, He J, Gong W, Zheng L, Chen S, Li B, et al: LncRNA HULC triggers autophagy via stabilizing Sirt1 and attenuates the chemosensitivity of HCC cells. Oncogene. 36:3528–3540. 2017. View Article : Google Scholar : PubMed/NCBI

105 

Wang C, Jiang X, Li X, Song S, Meng Q, Wang L, Lu Y, Xin X, Pu H, Gui X, et al: Long noncoding RNA HULC accelerates the growth of human liver cancer stem cells by upregulating CyclinD1 through miR675-PKM2 pathway via autophagy. Stem Cell Res Ther. 11:82020. View Article : Google Scholar : PubMed/NCBI

106 

Ghafouri-Fard S, Khoshbakht T, Taheri M and Shojaei S: A review on the role of small nucleolar RNA host gene 6 long non-coding RNAs in the carcinogenic processes. Front Cell Dev Biol. 9:7416842021. View Article : Google Scholar : PubMed/NCBI

107 

Jing Z, Ye X, Ma X, Hu X, Yang W, Shi J, Chen G and Gong L: SNGH16 regulates cell autophagy to promote sorafenib resistance through suppressing miR-23b-3p via sponging EGR1 in hepatocellular carcinoma. Cancer Med. 9:4324–4338. 2020. View Article : Google Scholar : PubMed/NCBI

108 

Raveh E, Matouk IJ, Gilon M and Hochberg A: The H19 long non-coding RNA in cancer initiation, progression and metastasis-a proposed unifying theory. Mol Cancer. 14:1842015. View Article : Google Scholar : PubMed/NCBI

109 

Zhang C, Xu SN, Li K, Chen JH, Li Q and Liu Y: The biological and molecular function of LINC00665 in human cancers. Front Oncol. 12:8860342022. View Article : Google Scholar : PubMed/NCBI

110 

Shan Y and Li P: Long intergenic non-protein coding RNA 665 regulates viability, apoptosis, and autophagy via the MiR-186-5p/MAP4K3 axis in hepatocellular carcinoma. Yonsei Med J. 60:842–853. 2019. View Article : Google Scholar : PubMed/NCBI

111 

Hong F, Gao Y, Li Y, Zheng L, Xu F and LI X: Inhibition of HIF1A-AS1 promoted starvation-induced hepatocellular carcinoma cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy. World J Surg Oncol. 18:1132020. View Article : Google Scholar : PubMed/NCBI

112 

ZHANG Y, Shi J, Luo J, Liu C and Zhu L: Regulatory mechanisms and potential medical applications of HNF1A-AS1 in cancers. Am J Transl Res. 14:4154–4168. 2022.PubMed/NCBI

113 

Liu Z, Wei X, Zhang A, Li C, Bai J and Dong J: Long non-coding RNA HNF1A-AS1 functioned as an oncogene and autophagy promoter in hepatocellular carcinoma through sponging hsa-miR-30b-5p. Biochem Biophys Res Commun. 473:1268–1275. 2016. View Article : Google Scholar : PubMed/NCBI

114 

Zhang X and Zhu Y: Research progress on regulating LncRNAs of hepatocellular carcinoma stem cells. Onco Targets Ther. 14:917–927. 2021. View Article : Google Scholar : PubMed/NCBI

115 

Wang X, Cheng ML, Gong Y, Ma WJ, Li B and Jiang YZ: LncRNA DANCR promotes ATG7 expression to accelerate hepatocellular carcinoma cell proliferation and autophagy by sponging miR-222-3p. Eur Rev Med Pharmacol Sci. 24:8778–8787. 2020.PubMed/NCBI

116 

Xiao H, Zhang F, Zou Y, Li J, Liu Y and Huang W: The function and mechanism of long non-coding RNA-ATB in cancers. Front Physiol. 9:3212018. View Article : Google Scholar : PubMed/NCBI

117 

Wang CZ, Yan GX, Dong DS, Xin H and Liu ZY: LncRNA-ATB promotes autophagy by activating Yes-associated protein and inducing autophagy-related protein 5 expression in hepatocellular carcinoma. World J Gastroenterol. 25:5310–5322. 2019. View Article : Google Scholar : PubMed/NCBI

118 

Peng N, He J, LI J, Huang H, Huang W, Liao Y and Zhu S: Long noncoding RNA MALAT1 inhibits the apoptosis and autophagy of hepatocellular carcinoma cell by targeting the microRNA-146a/PI3K/Akt/mTOR axis. Cancer Cell Int. 20:1652020. View Article : Google Scholar : PubMed/NCBI

119 

Yuan P, Cao W, Zang Q, Li G, Guo X and Fan J: The HIF-2α-MALAT1-miR-216b axis regulates multi-drug resistance of hepatocellular carcinoma cells via modulating autophagy. Biochem Biophys Res Commun. 478:1067–1073. 2016. View Article : Google Scholar : PubMed/NCBI

120 

Shi J, Guo C and Ma J: CCAT2 enhances autophagy-related invasion and metastasis via regulating miR-4496 and ELAVL1 in hepatocellular carcinoma. J Cell Mol Med. 25:8985–8996. 2021. View Article : Google Scholar : PubMed/NCBI

121 

Hussen BM, Azimi T, Abak A, Hidayat HJ, Taheri M and Ghafouri-Fard S: Role of lncRNA BANCR in human cancers: An updated review. Front Cell Dev Biol. 9:6899922021. View Article : Google Scholar : PubMed/NCBI

122 

Zhou M, Zhang G, Hu J, Zhu Y, Lan H, Shen X, Lv Y and Huang L: Rutin attenuates sorafenib-induced chemoresistance and autophagy in hepatocellular carcinoma by regulating BANCR/miRNA-590-5P/OLR1 axis. Int J Biol Sci. 17:3595–3607. 2021. View Article : Google Scholar : PubMed/NCBI

123 

Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK and Kjems J: Natural RNA circles function as efficient microRNA sponges. Nature. 495:384–388. 2013. View Article : Google Scholar : PubMed/NCBI

124 

Shang Q, Yang Z, Jia R and Ge S: The novel roles of circRNAs in human cancer. Mol Cancer. 18:62019. View Article : Google Scholar : PubMed/NCBI

125 

Li Z, Huang C, Bao C, Chen L, Lin M, Wang X, Zhong G, Yu B, Hu W, Dai L, et al: Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 22:256–264. 2015. View Article : Google Scholar : PubMed/NCBI

126 

Zhang Z, Zhang J, Diao L and Han L: Small non-coding RNAs in human cancer: Function, clinical utility, and characterization. Oncogene. 40:1570–1577. 2021. View Article : Google Scholar : PubMed/NCBI

127 

Morais P, Adachi H and Yu YT: Spliceosomal snRNA epitranscriptomics. Front Genet. 12:6521292021. View Article : Google Scholar : PubMed/NCBI

128 

Matera AG, Terns RM and Terns MP: Non-coding RNAs: Lessons from the small nuclear and small nucleolar RNAs. Nat Rev Mol Cell Biol. 8:209–220. 2007. View Article : Google Scholar : PubMed/NCBI

129 

Janin M, Coll-SanMartin L and Esteller M: Disruption of the RNA modifications that target the ribosome translation machinery in human cancer. Mol Cancer. 19:702020. View Article : Google Scholar : PubMed/NCBI

130 

Liang J, Wen J, Huang Z, Chen XP, Zhang BX and Chu L: Small nucleolar RNAs: Insight into their function in cancer. Front Oncol. 9:5872019. View Article : Google Scholar : PubMed/NCBI

131 

Cuciniello R, Filosa S and Crispi S: Novel approaches in cancer treatment: Preclinical and clinical development of small non-coding RNA therapeutics. J Exp Clin Cancer Res. 40:3832021. View Article : Google Scholar : PubMed/NCBI

132 

Novina CD and Sharp PA: The RNAi revolution. Nature. 430:161–164. 2004. View Article : Google Scholar : PubMed/NCBI

133 

Ozata DM, Gainetdinov I, Zoch A, O'Carroll D and Zamore PD: PIWI-interacting RNAs: small RNAs with big functions. Nat Rev Genet. 20:89–108. 2019. View Article : Google Scholar : PubMed/NCBI

134 

Liu Y, Dou M, Song X, Dong Y, Liu S, Liu H, Tao J, Li W, Yin X and Xu W: The emerging role of the piRNA/piwi complex in cancer. Mol Cancer. 18:1232019. View Article : Google Scholar : PubMed/NCBI

135 

Su Z, Wilson B, Kumar P and Dutta A: Noncanonical roles of tRNAs: tRNA fragments and beyond. Annu Rev Genet. 54:47–69. 2020. View Article : Google Scholar : PubMed/NCBI

136 

Zhang B, Liu Z, Cao K, Shan W, Liu J, Wen Q and Wang R: Circ-SPECC1 modulates TGFβ2 and autophagy under oxidative stress by sponging miR-33a to promote hepatocellular carcinoma tumorigenesis. Cancer Med. 9:5999–6008. 2020. View Article : Google Scholar : PubMed/NCBI

137 

Zhao Z, He J and Feng C: CircCBFB is a mediator of hepato-cellular carcinoma cell autophagy and proliferation through miR-424-5p/ATG14 axis. Immunol Res. 70:341–353. 2022. View Article : Google Scholar : PubMed/NCBI

138 

Han H, Yang C, Ma J, Zhang S, Zheng S, Ling R, Sun K, Guo S, Huang B, Liang Y, et al: N7-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the RPTOR/ULK1/autophagy axis. Nat Commun. 13:14782022. View Article : Google Scholar : PubMed/NCBI

139 

Li L and Chang HY: Physiological roles of long noncoding RNAs: Insight from knockout mice. Trends Cell Biol. 24:594–602. 2014. View Article : Google Scholar : PubMed/NCBI

140 

Pang KC, Frith MC and Mattick JS: Rapid evolution of noncoding RNAs: Lack of conservation does not mean lack of function. Trends Genet. 22:1–5. 2006. View Article : Google Scholar : PubMed/NCBI

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Volume 49 Issue 6

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Wu J, Zhu Y, Cong Q and Xu Q: Non‑coding RNAs: Role of miRNAs and lncRNAs in the regulation of autophagy in hepatocellular carcinoma (Review). Oncol Rep 49: 113, 2023
APA
Wu, J., Zhu, Y., Cong, Q., & Xu, Q. (2023). Non‑coding RNAs: Role of miRNAs and lncRNAs in the regulation of autophagy in hepatocellular carcinoma (Review). Oncology Reports, 49, 113. https://doi.org/10.3892/or.2023.8550
MLA
Wu, J., Zhu, Y., Cong, Q., Xu, Q."Non‑coding RNAs: Role of miRNAs and lncRNAs in the regulation of autophagy in hepatocellular carcinoma (Review)". Oncology Reports 49.6 (2023): 113.
Chicago
Wu, J., Zhu, Y., Cong, Q., Xu, Q."Non‑coding RNAs: Role of miRNAs and lncRNAs in the regulation of autophagy in hepatocellular carcinoma (Review)". Oncology Reports 49, no. 6 (2023): 113. https://doi.org/10.3892/or.2023.8550