miRNAs are small, non-protein-coding RNAs that produce ~22 nucleotide-long sequences. These mediate post-transcriptional gene suppression via the inhibition of protein translation or the destabilization of target transcription, by recognizing the 3′untranslated region (UTR) of homologous mRNAs. Among the miRNAs, LIN-4 was the first to be discovered (24). Subsequently, additional miRNAs and their corresponding functions have been studied, and a miRNA database has been established (25). This database provides a unique name to a miRNA prior to its discovery, and the sequences of all published miRNAs are included. In total, ~25% of human miRNA genes are located in the introns of precursor miRNAs (pre-mRNAs), suggesting that the majority of miRNAs are not transcribed from their own promoters but are instead processed from introns (26). As illustrated in Fig. 1, the transcription of miRNAs is often carried out by RNA polymerase II, and the transcript is further processed using capping and polyadenylation (27). Two successive processing reactions transform transcripts into mature miRNAs (28). In mammals, one of the processing reactions involves he removal of stem rings from the rest of the pri-miRNA transcript in the nucleus. This is carried out by nuclear members of Drosha to create pre-miRNA products (27). The second process includes the active transportation of pre-miRNAs out of the nucleus via output receptor and RAS-related nuclear protein (RAN)-GTP. In the cytoplasm, the terminal ring is removed from the stem of pre-miRNA by Dicer, to create a mature miRNA double-stranded body with a length of ~22 base pairs (26,27). The mature miRNA double strand is an unstable entity; it is at a high speed when bound to the Argonaute (AGO) protein. Only one strand is retained, depending on the relative thermodynamic stability of the ends of each strand (28).

miRNAs bind to AGO and GW182 proteins to form RNA-induced silencing complexes (RISCs), that mediate gene expression and participate in various biologically critical processes (29). Notably, this process involves two mechanisms. Firstly, the target RNA contains sequences entirely complementary to miRNA, and is cleaved by ribonuclease in the RISC complex (30,31). Moreover, when the target RNA includes sequences that are not entirely complimentary to the miRNA, these are controlled in translation (30,32). Through these mechanisms, miRNAs are involved in multifarious biological impacts, such as cell growth, cell death, cell differentiation, cell apoptosis, intercellular signaling and cell metabolism, including fat metabolism (26,33-35). The present review will focus on the steps of glycolysis in gynecological tumor cells in which miRNAs are involved.

Otto Heinrich Warburg (36,37) initially discovered the Warburg effect in the 1920s. This effect refers to the tendency of tumor cells to produce adenosine triphosphate (ATP) through anaerobic glycolysis, even when sufficient oxygen is present (36,37). Normal cellular glucose metabolism can be divided into two phases and ten reactions. The first phase is the production of two propanose phosphates from glucose and the second phase is the conversion of propanose phosphate to pyruvate. The specific process displayed in Fig. 2. Under aerobic conditions, pyruvate is further oxidized and decomposed to form acetyl CoA in the mitochondria, which can be wholly oxidized into H₂O and CO_2, through the electron transfer chain and Krebs cycle to generate ATP (38). Pyruvate cannot be further oxidized in anoxic conditions and is reduced to lactate.

Despite sufficient levels of oxygen in tumor cells, the cells continue to turn pyruvate into lactic acid, which is known as aerobic glycolysis. In addition, tumor cells exhibit an increased glucose uptake. Therefore, the production of lactic acid by pyruvate increases and the pH value of tumor cells l decreases. The results of a previous study demonstrated that this may be due to tumor cells living in environments rich in glucose and other nutrients, indicating that there is no ATP deficiency. On the other hand, tumor cells may convert all glucose into CO_2, through oxidative phosphorylation, which maximizes ATP production but does not meet the requirements of rapid cell proliferation. Notably, the rapid proliferation of tumor cells requires numerous substances, such as nucleotides, lipids and amino acids (39). In addition, glucose produces acetyl coenzyme A and ribose, which are used for nucleotide biosynthesis for rapid DNA replication (40,41). However, the requirements of the Warburg effect in cancer have yet to be fully elucidated (41-43).

Using dual-luciferase and bioinformatics analyses, the results of previous studies revealed PFKFB3 as a rate-limiting enzyme that regulates glycolysis. In addition, the levels of PFKFB3 are significantly increased in a variety of human tumors, ultimately expanding the glycolysis levels of tumor cells, and the corresponding levels of proliferation and metastasis (92,93). miR-206 interacts directly with the 3′UTR of PFKFB3 mRNA. The overexpression of miR-206 obstructs the production of fructose-2,6-bisphosphatase (F-2, 6-BP), reduces lactic acid production, and reduces cell propagation and tumor migration (94). In other types of cancer, such as colorectal cancer, miR-488 directly targets PFKFB3, and PFKFB3 mRNA levels are inhibited by miR-488. This results in decreased glucose uptake and lactate secretion, increased sensitivity to chemotherapy drugs, and decreased proliferation, invasion, and migration (95,96). miR-3666 and miR-26b also reduce the rate of glycolysis through inhibiting the activity of PFKFB3; thus, contributing to tumor inhibition (97,98).

PDK phosphorylates pyruvate dehydrogenase and converts glucose metabolism from OXPHOS to glycolysis, resulting in increased lactate production. There are four subtypes of PDK in human cells (PDK1, PDK2, PDK3 and PDK4), each highly expressed in different tumors. The results of a dual-luciferase reporter gene assay demonstrated that miRNA-9, as a tumor suppressor, directly targets PDK1, reduces the levels of glycolysis and inhibits the development of prostate cancer (99). miR-4290 has been shown to enhance cisplatin sensitivity in gastric cancer cells by inhibiting PDK1-mediated glycolysis (100). miRNA-375 was the most downregulated miRNA in gastric cancer cells, and its ectopic expression significantly inhibited cell survivability through a caspase-mediated apoptosis pathway. Moreover, high miR-375 expression levels inhibited the expression of PDK1 (101). In nasopharynx cancer, PDK1 is the target of miR-375, and tumor development is negatively associated with miR-375 expression levels (102). The results obtained from the Interactive Analysis of Gene Expression Profiling database demonstrated that PDK1 levels were markedly increased in glioma tissues. The downstream target of miR-128-3p is PDK1, and miR-128-3p overexpression interfered with the Warburg effect in neuroglioma cells by decreasing PDK1 expression, and inhibiting the occurrence and development of glioma (103).

In TNBC cells, PDK4, as a downstream target of miR-136-5p, has been found to be downregulated, subsequently reducing the Warburg effect and inhibiting the proliferation and metastasis of TNBC cells (104). In cervical cancer, miR-16-5p targets PDK4 to reduce glycolysis levels and chemical resistance (105). Other human tumor cells that also target PDK4 and inhibit expression include miR-21 (106), miR-9-5p (107) and miR-5683 (108).

In gastric cancer tissues, PDK3 levels are increased, and miR-497-5p directly downregulates PDK3, thereby inhibiting the proliferation and growth of cells (109).

p53 is one of the most common tumor suppressor genes. In the process of normal development, p53 activity is often low. p53 pathway deactivation occurs in tumors, as it functions in inhibiting cell proliferation and in controlling metabolism. Thus, p53 plays a role in resisting high levels of glycolysis of tumor cells, and aiding in the adaptation to metabolic stress. p53 activity aids in preventing the occurrence and development of cancer, and provides a basis for the development of novel tumor therapies (110-112).

The activation of p53 induces a variety of non-coding miRNAs, including miR-34a. The results of previous studies demonstrated that p53 overexpression reduces the expression levels of HK2, pyruvate kinase M (PKM), phosphofructokinase 1 (PFKP), PFKFB3 and hypoxia-inducible factor-1α (HIF-1α) in cells, by inducing the upregulation of miR-34a expression; thus, inhibiting the Warburg effect. This ultimately impacts the proliferation and metastasis of tumor cells (113). TP53-inducible glycolysis and apoptosis regulator (TIGAR), an apoptosis and glycolysis regulatory factor, is a downstream target of p53, that controls cell metabolism and prevents programmed cell death. TIGAR primarily functions as a F-2, 6-BP to inhibit the Warburg effect. In liver tumors, miR-885-5p and the associated precursors bind to TIGAR promoter binding sites, alter local chromatins construction, and subsequently adjust the levels of TIGAR (114,115). miR-125b is a negative regulator of p53 (112). Other miRNAs that act on p53, such as miR-504, miR-25 and miR-30d, inhibit its expression by directly binding to the 3′UTR of p53 mRNA. By contrast, miR-34, miR-215, miR-194, miR-605, miR-192 and miR-29 affect the regulation of p53, leading to the indirect activation of p53 (116).

C-myc is an oncogenic transcription factor that is overexpressed in numerous cancer types, and is involved in cell metabolism and proliferation processes, including nucleotide metabolism, glucose metabolism and, glutamine metabolism. Notably, c-myc also participates in ribosomal and mitochondrial biogenesis. Myc functions as an oncogene in the development of numerous human cancers (117,118). Therefore, the inhibition of c-myc may exhibit potential in glucose metabolism in tumor cells, thus providing a basis for the development of novel treatment option (118).

The results of previous studies have demonstrated an association between c-myc and miRNAs. For example, miR-222-3p indirectly activates c-myc and c-myc target genes, such as GULT1, HK2 and lactate dehydrogenase A (LDHA) (119). miR-644a directly inhibits c-myc, thereby inhibiting the Warburg effect and proliferation (120). Through miRNA target prediction, c-myc was identified as a potential target of Let-7a, which inhibits the glucose metabolism activity of tumor cells through inhibiting c-myc (121). miR-3679-5p indirectly regulates c-myc by inhibiting the transcription of neuronal precursor cell-expressed developmentally downregulated 4, an E3 ligase, leading to c-myc stability and Warburg effect increases, thus driving chemical resistance in lung cancer (122). The results of a previous study demonstrated that miR-155-deficient cells possess reduced genes that play a role in the Warburg effect, and exhibit reduced HK2, LDHA and PKM2 expression levels. Further results demonstrated that the downregulation of c-myc controls the PIK3R1-PDK1/Akt-Foxo3a pathway; however, there is no miR-155 binding domain in c-myc. These associations have yet to be fully elucidated (123).

AMPK plays a role as a metabolic master switch, regulating three major types of metabolisms in metabolic tissues, such as muscles and the liver. AMPK is also a stabilizer of organic energy in cells. AMPK harmonizes and balances various metabolic pathways, including glucose uptake and mitochondrial biogenesis, and ultimately regulates cell and organ tissue growth (124).

The results of previous studies demonstrated that the human tumor suppressor, liver kinase B1 (LKB1), directly activates AMPK by encoding serine/threonine kinases, suggesting that the LKB1-AMPK axis may be an essential cancer inhibitory pathway (125,126). Epstein Barr virus (EBV)-miR-bart1-5p, a miRNA encoded by EBV-Barts, binds to the α1 telomerase of AMPK (AMPKα1). This activates the mTOR/HIF1 pathway to affect angiogenesis, leading to angiogenesis and glycolysis in tumor cells. This leads to the propagation, transfer and migration of tumor cells (127). The results of a previous study demonstrated that miR-27a inhibited the AMPK pathway, enhanced mTOR signaling, and functioned synergistically with oncogenes and tumor cell metabolic regulators, leading to enhanced glycolysis, unrestricted growth and chemical resistance (128). By contrast, aryl camphor flavone increased miR-124-3p expression in glioma cells by activating the reactive oxygen species (ROS)/AMPK signaling pathway, inducing apoptosis and inhibiting cell glycolysis (129).

AKT, also known as protein kinase B, is a serine/threonine kinase with three subtypes in mammalian cells. AKT is stimulated by various growth factors to become phosphorylated (p-)AKT, which affects multiple cellular functions and is a crucial regulator of pro-growth signals (130). The results of a previous study demonstrated that increased AKT and p-AKT expression levels were associated with the appearance, development and prognosis of various human tumors (131). Another study verified that proteins of the PI3K/AKT/mTOR signaling pathway were highly expressed in tumors (130). This pathway regulates essential processes in tumor cell development, such as substance metabolism and cytoskeletal remodeling metastasis. The reduced activity of the PI3K/AKT/mTOR signaling pathway decreases the levels of glycolysis in tumor cells. Notably, miR-21 and miR-520a-3p act by reducing the expression levels of PKM2 and LDHA in the glycolysis pathway to reduce glycolysis in tumor cells (132,133). In addition, miR-485-3p binds to AKT3 mRNA and downregulates glycol- and migration-associated proteins expression by suppressing the activation of the AKT3/mTOR pathway, and inhibiting cell glycolysis, propagation and migration (134).

As a PTEN binding protein, N-myc downstream-regulated gene 2 (NDRG2) regulates PTEN phosphatase through dephosphorylation. In addition, PIP3, the primary substrate of PTEN, phosphorylates AKT. Thus, PTEN/PI3K/AKT is an essential axis for controlling propagation, migration and metabolism (135). miR-181a-5p binds to NDRG2 and promotes migration and glycolysis through stimulating the PTEN/AKT axis, ultimately leading to a poor prognosis (136).

Insulin-like growth factor-1 receptor (IGF-1R) is a carcinogen that stimulates cell propagation and metabolism and is upregulated in numerous tumors. miRNA-342-3p and miR-7 inhibit the IGF-1R-mediated PI3K/AKT/GLUT1 signaling pathway through directly binding with the 3′UTR of IGF-1R; thus, reducing glucose uptake (137,138).

As presented in Table I, various miRNAs play differential roles in the glycolysis of ovarian cancer cells. The results of a previous study demonstrated that the levels of lncRNA-NEAT1 in ovarian cancer were notably increased, and the proliferation, invasion and glycolysis of ovarian cancer were markedly inhibited following NEAT1 knockdown (139). In addition, StarBase database prediction and a dual-luciferase reporter assay were used to verify that NEAT1 was the sponge of miR-4500, and alkaline leucine zipper and w2-domain protein 1 (BZW1) were direct targets of miR-4500. miR-4500 silencing reversed the suppressive effects of NEAT1 knockdown on ovarian cancer, whereas the overexpression of BZW1 reversed the suppressive effects of miR-4500 on the tumor. Notably, NEAT1 accelerated the occurrence and development of ovarian cancer via the miR-4500/BZW1 axis. Thus, NEAT1 may exhibit potential in the treatment of ovarian cancer; however, further investigations are required (139). lncRNA OPA-interacting protein 5 antisense transcript 1 (lncRNA-OIP5-AS1) is also elevated in ovarian cancer. As previously demonstrated, OIP5-AS1 knockdown inhibited the migration and glycolysis of ovarian cancer, and accelerated programmed cell death. The results obtained using StarBase, TargetScan and a dual-luciferase reporter assay demonstrated that OIP5-AS1 indirectly regulated cyclin G1 (CCNG1) levels by sponging miR-128-3p. Moreover, miR-128-3p suppressed the progression of numerous cancers (140,141). Subsequent experiments demonstrated that miR-128-3p knockdown alleviated the decrease in glucose consumption and lactic acid production, enhanced apoptosis, and prevented cell migration caused by CCNG1 knockdown. These results demonstrated that OIP5-AS1 functions as a carcinogen in the development of ovarian cancer through the miR-128-3p/CCNG1 axis, which may act as a basis for the development of novel therapeutic options for ovarian cancer (142). The results of an RT-qPCR analysis demonstrated that lncRNA-LINC00504 expression was upregulated in ovarian cancer. In addition, the results of further assays demonstrated that LINC00504 was overexpressed in ovarian cancer, which promoted cell proliferation and upregulated PDK1, PKM2 and HK2, thereby increasing the levels of glycolysis in cells. Moreover, LINC00504 reduced the expression of miR-1244 through sponging. In summary, LNC00504 promotes ovarian cancer cell development and glycolysis through targeting miR-1244, suggesting that LINC00504 may function as a therapeutic target for ovarian cancer (143).

Previous research has demonstrated that the Hippo signaling pathway is associated with tumor development. As a critical oncogene of the Hippo pathway (144,145), yes1-associated transcriptional regulator (YAP1) is targeted by miR-486-5p, and miR-486-5p binds to LINC00857 in ovarian cancer, and inhibits the progression and glycolysis of ovarian cancer. Thus, LINC00857 inactivates the Hippo pathway. Notably, LINC00857 regulates ovarian cancer development through sponging miR-486-5p and upregulating YAP1, through regulation of the Hippo signaling pathway (146).

miR-29b functions as a tumor inhibitor in numerous types of cancer, and the expression of this miRNA was reduced in epithelial ovarian cancer (147). Using dual-luciferase reporter gene detection, the results demonstrated that miR-29b bound directly to AKT2/AKT3 3′UTR and inhibited the corresponding expression. Activated AKT promotes GLUT and HK expression, to increase the activity of phosphofructokinase (148); thus, stimulating the glucose to lactic acid metabolism pathway. This ultimately promotes the replication and migration of tumor cells. Therefore, it was hypothesized that miR-29b may negatively regulate AKT to reduce glycolysis levels and inhibit tumor development in epithelial ovarian cancer. The results of a previous study demonstrated that miR-29b silencing upregulated the mRNA expression of AKT2/3, PKM2 and HK2, and increased glucose intake and lactate production in ovarian cancer cells. On the other hand, miR-29b overexpression demonstrated the reverse effects (147). Thus, these results demonstrated that miR-29b plays a key role in regulating the Warburg effect, and in the replication and migration of ovarian cancer cells through impacting the expression of AKT. This may provide a theoretical basis for the development of novel treatment options for epithelial ovarian cancer.

The results of previous studies demonstrated that PFKFB3 was overexpressed in human cancers, such as in ovarian cancer, where the upregulation of PFKFB3 expression promoted cell growth and migration and enhanced chemotherapeutic resistance (149,150). Using a dual-luciferase assay, the results of a previous study demonstrated that miR-206 reduced the levels of PFKFB3 by binding with the 3′UTR, miR-206 overexpression prevented the proliferation and migration of ovarian cancer by downregulating the PFKFB3 levels. In addition, the results of another study demonstrated that miR-206 downregulated PFKFB3 expression and negatively regulated focal adhesion kinase (FAK) post-transcription. These results indicated that miR-206 exhibits numerous roles, and may be used to control ovarian cancer characterized by FAK overexpression and resistance to chemotherapy (93).

Mitochondrial calcium uptake 1 (MICU1) is a protein in the inner membrane of the mitochondria that inhibits calcium ions from entering. However, in ovarian cancer, MICU1 overexpression increases glycolysis and enhances cellular chemotherapy resistance. Moreover, MICU1 plays a role in the low survival rates of patients with ovarian cancer (151), highlighting its potential use as a target in the treatment of ovarian cancer. miR-195 is a tumor inhibitor in various types of cancer (152,153), and its expression is reduced in seven different ovarian cancer cell lines (OVCAR4, A2780-CP20, TYK-NU(JCRB0234.0), TYK-NU.CPr(JCRB0234.1), OVSAHO(JCRB1046), ATCC CRL-11732™ and FTE188). Notably, MICU1 expression was significantly increased in six of these cancer cells, compared with standard cell lines (152). It was demonstrated that miR-195 targeted the MICU1 3′UTR in healthy cells, leading to decreased MICU1 expression. Moreover, intracellular lactic acid levels were significantly reduced in ovarian cancer cell lines following miR-195 overexpression or MICU1 knockdown, suggesting that glycolysis was inhibited (154). It was also demonstrated that miR-195 expression levels maintained calcium homeostasis and reduced the glycolysis of ovarian cancer cells by regulating MICU1; thus, inhibiting cell growth and migration. Tumor growth experiments in female athymic mice revealed that miR-195 prolonged the in vivo survival of ovarian cancer models in mice, and the re-expression of MICU1 in cells reversed the tumor growth-inhibiting phenotype caused by miR-195 overexpression. These results suggest that miR-195 extends overall survival in ovarian cancer patients by targeting MICU1 (154). In addition, lncRNA component of mitochondrial RNA processing endoribonuclease (lncRNA-RMRP) functions as a tumor activator in various types of cancer (155,156), and also increases MICU1 expression by sponging miR-580-3p, thus promoting glycolysis and paclitaxel resistance in ovarian cancer (157).

Similarly, miR-383, miR-603 and miR-132 are inhibitors of several human cancers, and their expression levels are significantly decreased. The results of previous studies demonstrated that the ectopic levels of miR-383 inhibit LDHA mRNA expression by binding with the 3′UTR of LDHA. Moreover, miR-603 directly targets HK2 expression. miR-132 affects PI3K and TGFβ signaling pathways or Ras, AKT and mTOR oncogene expression. Notably, these miRNAs promote cell apoptosis, reduce glucose consumption and lactic acid production, and inhibit cell proliferation and invasion (86,158,159).

By contrast, miR-203 and miR-1180 expression have been shown to be increased in ovarian cancer tissues, compared with healthy tissues. miR-203 mainly targets the 3′UTR of pyruvate dehydrogenase B, while secreted frizzled-related protein 1, a tumor inhibitor (160), acts as a direct target gene of miR-1180, and activates the Wnt signaling pathway following miR-1180-induced inhibition (161,162). Notably, miRNAs promote glucose consumption and lactate production in tumor cells to increase glycolysis. This leads to cell colony growth, migration and invasion (163).

The roles of numerous miRNAs in the development of cervical cancer are presented in Table II. The results of a previous study demonstrated that hypoxic-responsive lncRNA-TDRG1 expression was increased in cervical cancer. Subsequently, the interactive association between miR-214-5p, lncRNA-TDRG1 and signaling SEMA4C was analyzed. The levels of lncRNA-TDRG1, miR-214-5p, SEMA4C and HK2 were evaluated using western blot analysis and RT-qPCR. Under conditions of hypoxia, lncRNA-TDRG1 knockdown inhibited glycolysis and the migration of cervical cancer. Moreover, miR-214-5p knockdown or SEMA4C overexpression reversed tumor inhibition. In conclusion, lncRNA-TDRG1 acts on miR-214-5p to affect SEMA4C expression, glycolysis and the migration of cervical cancer cells (50). Compared with healthy cells, NEAT1 expression levels have been found to be increased in cervical cancer cells, which affect the levels of miR-34a, leading to dysglycolysis and 5-fluorouracil resistance. Bioinformatics prediction using TargetScan revealed that LDHA was a close target of miR-34a-5p, and miR-34a and LDHA mRNA expression were negatively correlated. The NEAT1-mediated miR-34a/LDHA axis may act as a latent treatment for chemotherapy-resistant cervical cancer (164). lncRNA-OIP5-AS1 is considered a hypoxic-responsive lncRNA. In addition, OIP5-AS1 inhibits miR-124-5p to promote Isocitrate dehydrogenase 2 (IDH2) expression, and IDH2 promotes the Warburg effect in cervical cancer cells through regulating HIF-1α expression (165).

Inositol polyphosphate 1-phosphatase (INPP1) is an enzyme involved in glycolysis and lipid metabolism. Using RT-qPCR, the results demonstrated that INPP1 mRNA expression was increased in cervical cancer. In addition, INPP1 overexpression enhanced cell viability and facilitated cell irradiation. Results of wound healing and translocation assays demonstrated that migration and invasion rates were significantly increased following INPP1 was overexpression. Moreover, results of a dual-luciferase reporter assay demonstrated that miR-27a binds with the 3′UTR of INPP. miR-27a is highly expressed in a variety of cancer cells and is essential in the invasion of cancer (166-168). The results of a previous study demonstrated that miR-27a expression was increased cervical cancer, and was positively associated with INPP1. Notably, miR-27a is upregulated in cervical cancer cells and promotes the overexpression of INPP1. This regulates cell metabolic reprogramming and promotes aerobic glycolysis, ultimately increasing the viability of cervical cancer cells (169). Thus, miR-27a and INPP1 may function as potential biomarkers for cervical cancer.

By contrast, miR-34a expression is often reduced in tumors (170,171), and plays a crucial role in tumor suppression. Notably, miR-34a regulates a variety of target genes involved in cell replication, differentiation and apoptosis, and interferes with the processes involved in cancer cell metastasis and chemical tolerance (172). The results of the measurement of lactate production and glucose consumption demonstrated that cervical cancer cells with exogenous miR-34a consume less glucose, highlighting that miR-34a prevents the aerobic glycolysis of cervical cancer cells (173). The results obtained using the miRNA target prediction program, miRbase, demonstrated that LDHA is a downstream target of miR-34a. In addition, the ectopic expression of miR-34a or LDHA knockdown reduced tumor growth and invasion (173). Thus, it was hypothesized that miR-34a may play an inhibitory role in cervical cancer, and may exhibit potential in the treatment of cervical cancer.

The results of a previous study demonstrated that miRNA-497 regulated ROS and glutathione levels by targeting the transketolase enzyme involved in the pentose phosphate pathway and subsequently promoting cisplatin chemical resistance in cervical cancer (174). miR-16-5p directly binds to PDK4. The inhibition of miR-16-5p has been shown to lead to an increased expression of PDK4, which activates glycolytic metabolic activity and enhances chemoresistance in cervical cancer (105). Therefore, miR-497 and miR-16-5p may exhibit potential as targets in the treatment of chemical resistance in cervical cancer.

The roles of miRNAs in endometrial cancer are presented in Table III. Notably, HK2 is upregulated in various types of cancer, such as endometrial cancer. HK2 expression is significantly increased in high-risk endometrial cancer cells, suggesting that HK2 expression is associated with the prognosis of endometrial cancer. Numerous prediction algorithms have revealed that miR-455 and miR-181a may bind to the 3′UTR of HK2, and miR-455 directly inhibits HK2 expression. In addition, lncRNA deleted in lymphocytic leukemia 2 (lncRNA-DLEU2) binds EZH2 and increases the corresponding expression while silencing miR-181a. Subsequently, this increases HK2 levels and promotes glycolysis (76). In conclusion, DLEU2 affects the progression of endometrial cancer through targeting the miR-455/HK2 and EZH2/miR-181a/HK2 axis, which may exhibit potential in the treatment of endometrial cancer.

At present, research focused on the expression of miRNAs in vulvar carcinoma is limited. The results of a previous study demonstrated that miR-182-5p, miR-183-5p and miR-590-5p were upregulated, and miR-103a-3p, miR-107 and miR-603 were downregulated in vulvar squamous cell carcinoma (175). Moreover, miR-19-b1-5p and miR-223-5p downregulation were previously found to be associated with the presence of lymph node metastasis (176). However, the role and molecular mechanisms of miRNAs in glycolysis, and their potential to predict treatment outcomes in patients with uterine sarcoma have yet to be fully elucidated. The results of a previous study demonstrated that the downregulation of miR-10a-5p and miR-125a-5p, and the upregulation of miR-34c-5p and miR-196a-5p were associated with the prognosis of patients with uterine leiomyosarcoma (177). In endometrial stromal sarcoma, the downregulation of miR-23-3p and let-7b-5p, and the upregulation of miR-372-3p and miR-373-3p were associated with poor survival outcomes. The expression levels of miR-210-3p, miR-301a-3p and miR-335-5p were increased in patients with tumor metastasis and recurrence (177).