lncRNA LOXL1‑AS1 promotes liver cancer cell proliferation and migration by regulating the miR‑377‑3p/NFIB axis

Yu,Wei; Dai,Yong

doi:10.3892/ol.2021.12885

lncRNA LOXL1‑AS1 promotes liver cancer cell proliferation and migration by regulating the miR‑377‑3p/NFIB axis

Authors:
- Wei Yu
- Yong Dai
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Affiliations: Department of General Surgery, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
Published online on: June 29, 2021 https://doi.org/10.3892/ol.2021.12885
Article Number: 624
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver cancer is becoming one of the most lethal malignancies due to its high incidence and mortality. Accumulating studies have indicated that long non‑coding RNAs (lncRNAs) are critical regulators of the tumorigenesis and development of various types of cancer, including liver cancer. LncRNA LOXL1‑antisense RNA 1 (LOXL1‑AS1) has been identified as an oncogene in some types of human cancer; however, its role in liver cancer remains obscure. Reverse transcription‑quantitative PCR was used to measure LOXL1‑AS1 expression in liver cancer tissues and cells. Western blot, MTT, colony formation, glucose uptake and wound healing assays were used to explore the biological function of LOXL1‑AS1 in liver cancer cells. Bioinformatics analysis and RNA pull‑down and luciferase reporter assays were used to explore the molecular mechanism of LOXL1‑AS1 in liver cancer cells. Statistical analysis was used to compare the experimental results of different groups. In the present study, LOXL1‑AS1 expression was significantly upregulated in liver cancer tissues and cells compared with in normal liver tissues and cells, respectively. High LOXL1‑AS1 expression was associated with poor clinical outcomes in patients with liver cancer. Furthermore, LOXL1‑AS1‑knockdown suppressed glucose metabolism, proliferation, migration and epithelial‑mesenchymal transition (EMT) of liver cancer cells. Subsequently, LOXL1‑AS1 acted as a microRNA (miR)‑377‑3p sponge, and nuclear factor I B (NFIB) was confirmed as the downstream target of miR‑377‑3p in liver cancer cells. Additionally, rescue assays suggested that NFIB overexpression countervailed the inhibitory influence of LOXL1‑AS1 silencing on liver cancer cellular processes. The present study demonstrated that LOXL1‑AS1 promoted glucose metabolism, proliferation, migration and EMT of liver cancer cells by sponging miR‑377‑3p and modulating NFIB, which may provide a novel insight for the treatment of liver cancer.

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1	Ding LJ, Li Y, Wang SD, Wang XS, Fang F, Wang WY, Lv P, Zhao DH, Wei F and Qi L: Long noncoding RNA lncCAMTA1 promotes proliferation and cancer stem cell-like properties of liver cancer by inhibiting CAMTA1. Int J Mol Sci. 17:16172016. View Article : Google Scholar : PubMed/NCBI
2	Gan HY, Li N, Zhang Q and Feng ZZ: Silencing FOXA1 gene regulates liver cancer cell apoptosis and cell proliferation. Eur Rev Med Pharmacol Sci. 22:397–404. 2018.PubMed/NCBI
3	Petruzziello A: Epidemiology of hepatitis B virus (HBV) and Hepatitis C virus (HCV) related hepatocellular carcinoma. Open Virol J. 12:26–32. 2018. View Article : Google Scholar : PubMed/NCBI
4	Robert J: Biology of cancer metastasis. Bull Cancer. 100:333–342. 2013.(In French). View Article : Google Scholar : PubMed/NCBI
5	Abdel-Misih SR and Bloomston M: Liver anatomy. Surg Clin North Am. 90:643–53. 2010. View Article : Google Scholar : PubMed/NCBI
6	Lu WP and Dong JH: Hepatectomy for hepatocellular carcinoma in the era of liver transplantation. World J Gastroenterol. 20:9237–9244. 2014.PubMed/NCBI
7	Islami F, Miller KD, Siegel RL, Fedewa SA, Ward EM and Jemal A: Disparities in liver cancer occurrence in the United States by race/ethnicity and state. CA Cancer J Clin. 67:273–289. 2017. View Article : Google Scholar : PubMed/NCBI
8	Ye Y, Shen A and Liu A: Long non-coding RNA H19 and cancer: A competing endogenous RNA. Bull Cancer. 106:1152–1159. 2019. View Article : Google Scholar : PubMed/NCBI
9	Fu XM, Guo W, Li N, Liu HZ, Liu J, Qiu SQ, Zhang Q, Wang LC, Li F and Li CL: The expression and function of long noncoding RNA lncRNA-ATB in papillary thyroid cancer. Eur Rev Med Pharmacol Sci. 21:3239–3246. 2017.PubMed/NCBI
10	Misawa A, Takayama K, Urano T and Inoue S: Androgen-induced long noncoding RNA (lncRNA) SOCS2-AS1 promotes cell growth and inhibits apoptosis in prostate cancer cells. J Biol Chem. 291:17861–17880. 2016. View Article : Google Scholar : PubMed/NCBI
11	Cui C, Zhai D, Cai L, Duan Q, Xie L and Yu J: Long noncoding RNA HEIH promotes colorectal cancer tumorigenesis via counteracting miR-939-mediated transcriptional repression of Bcl-xL. Cancer Res Treat. 50:992–1008. 2018. View Article : Google Scholar : PubMed/NCBI
12	Wang H, Huo X, Yang XR, He J, Cheng L, Wang N, Deng X, Jin H, Wang N, Wang C, et al: STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4. Mol Cancer. 16:1362017. View Article : Google Scholar : PubMed/NCBI
13	Jiao Y, Li Y, Ji B, Cai H and Liu Y: Clinical value of lncRNA LUCAT1 expression in liver cancer and its potential pathways. J Gastrointestin Liver Dis. 28:439–447. 2019. View Article : Google Scholar : PubMed/NCBI
14	Zhang Z, Wang S, Yang F, Meng Z and Liu Y: LncRNA ROR1AS1 high expression and its prognostic significance in liver cancer. Oncol Rep. 43:55–74. 2020.PubMed/NCBI
15	Li GH, Yu JH, Yang B, Gong FC and Zhang KW: LncRNA LOXL1-AS1 inhibited cell proliferation, migration and invasion as well as induced apoptosis in breast cancer via regulating miR-143-3p. Eur Rev Med Pharmacol Sci. 23:10400–10409. 2019.PubMed/NCBI
16	Li W, Zhang B, Jia Y, Shi H, Wang H, Guo Q and Li H: LncRNA LOXL1-AS1 regulates the tumorigenesis and development of lung adenocarcinoma through sponging miR-423-5p and targeting MYBL2. Cancer Med. 9:689–699. 2020. View Article : Google Scholar : PubMed/NCBI
17	Liu Y, Guo C, Li F and Wu L: LncRNA LOXL1-AS1/miR-28-5p/SEMA7A axis facilitates pancreatic cancer progression. Cell Biochem Funct. 38:58–65. 2020. View Article : Google Scholar : PubMed/NCBI
18	Li M, Cai O and Tan S: LOXL1-AS1 drives the progression of gastric cancer via regulating miR-142-5p/PIK3CA Axis. Onco Targets Ther. 12:11345–11357. 2019. View Article : Google Scholar : PubMed/NCBI
19	Xie N, Fei X, Liu S, Liao J and Li Y: LncRNA LOXL1-AS1 promotes invasion and proliferation of non-small-cell lung cancer through targeting miR-324-3p. Am J Transl Res. 11:6403–6412. 2019.PubMed/NCBI
20	Kee KM, Wang JH, Lin CY, Wang CC, Cheng YF and Lu SN: Validation of the 7th edition TNM staging system for hepatocellular carcinoma: An analysis of 8,828 patients in a single medical center. Dig Dis Sci. 58:2721–2728. 2013. View Article : Google Scholar : PubMed/NCBI
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
22	Li Z and Zhang H: Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression. Cell Mol Life Sci. 73:377–392. 2016. View Article : Google Scholar : PubMed/NCBI
23	Zhao J, Bai X, Feng C, Shang X and Xi Y: Long non-coding RNA HCP5 facilitates cell invasion and epithelial-mesenchymal transition in oral squamous cell carcinoma by miR-140-5p/SOX4 Axis. Cancer Manag Res. 11:10455–10462. 2019. View Article : Google Scholar : PubMed/NCBI
24	Wang J, Zhang C, Wu Y, He W and Gou X: Identification and analysis of long non-coding RNA related miRNA sponge regulatory network in bladder urothelial carcinoma. Cancer Cell Int. 19:3272019. View Article : Google Scholar : PubMed/NCBI
25	Denny SK, Yang D, Chuang CH, Brady JJ, Lim JS, Grüner BM, Chiou SH, Schep AN, Baral J, Hamard C, et al: Nfib promotes metastasis through a widespread increase in chromatin accessibility. Cell. 166:328–342. 2016. View Article : Google Scholar : PubMed/NCBI
26	Liu J, Zhai C, Liu D and Liu J: The long noncoding RNA LOXL1-AS1 promotes the proliferation, migration, and invasion in hepatocellular carcinoma. Anal Cell Pathol (Amst). 2020:41820922020.PubMed/NCBI
27	Yang X, Xing G, Liu S, Li B, He Y and Wang F: LncRNA LOXL1-AS1 promotes endometrial cancer progression by sponging miR-28-5p to upregulate RAP1B expression. Biomed Pharmacother. 125:1098392020. View Article : Google Scholar : PubMed/NCBI
28	Xue F, Xu YH, Shen CC, Qin ZL and Zhou HB: Non-coding RNA LOXL1-AS1 exhibits oncogenic activity in ovarian cancer via regulation of miR-18b-5p/VMA21 axis. Biomed Pharmacother. 125:1095682020. View Article : Google Scholar : PubMed/NCBI
29	Meng Q and Lan D: A review on muscle-specific microRNAs as the biomarker for Duchenne muscular dystrophy. Zhongguo Dang Dai Er Ke Za Zhi. 21:1148–1152. 2019.(In Chinese). PubMed/NCBI
30	He J, Zhao H, Deng D, Wang Y, Zhang X, Zhao H and Xu Z: Screening of significant biomarkers related with prognosis of liver cancer by lncRNA-associated ceRNAs analysis. J Cell Physiol. 235:2464–2477. 2020. View Article : Google Scholar : PubMed/NCBI
31	Zhang B, Zhou M, Zou L, Miao J, Wang Y, Li Y, Lu S and Yu J: Long non-coding RNA LOXL1-AS1 acts as a ceRNA for miR-324-3p to contribute to cholangiocarcinoma progression via modulation of ATP-binding cassette transporter A1. Biochem Biophys Res Commun. 513:827–833. 2019. View Article : Google Scholar : PubMed/NCBI
32	Long B, Li N, Xu XX, Li XX, Xu XJ, Liu JY and Wu ZH: Long noncoding RNA LOXL1-AS1 regulates prostate cancer cell proliferation and cell cycle progression through miR-541-3p and CCND1. Biochem Biophys Res Commun. 505:561–568. 2018. View Article : Google Scholar : PubMed/NCBI
33	Tang L, Yang B, Cao X, Li Q, Jiang L and Wang D: MicroRNA-377-3p inhibits growth and invasion through sponging JAG1 in ovarian cancer. Genes Genomics. 41:919–926. 2019. View Article : Google Scholar : PubMed/NCBI
34	Wang X, Chen T, Zhang Y, Zhang N, Li C, Li Y, Liu Y, Zhang H, Zhao W, Chen B, et al: Long noncoding RNA Linc00339 promotes triple-negative breast cancer progression through miR-377-3p/HOXC6 signaling pathway. J Cell Physiol. 234:13303–13317. 2019. View Article : Google Scholar : PubMed/NCBI
35	Ell B and Kang Y: Transcriptional control of cancer metastasis. Trends Cell Biol. 23:603–611. 2013. View Article : Google Scholar : PubMed/NCBI
36	Wilczynska KM, Singh SK, Adams B, Bryan L, Rao RR, Valerie K, Wright S, Griswold-Prenner I and Kordula T: Nuclear factor I isoforms regulate gene expression during the differentiation of human neural progenitors to astrocytes. Stem Cells. 27:1173–1181. 2009. View Article : Google Scholar : PubMed/NCBI
37	Wu C, Zhu X, Liu W, Ruan T, Wan W and Tao K: NFIB promotes cell growth, aggressiveness, metastasis and EMT of gastric cancer through the Akt/Stat3 signaling pathway. Oncol Rep. 40:1565–1573. 2018.PubMed/NCBI
38	Sun L, Fang Y, Wang X, Han Y, Du F, Li C, Hu H, Liu H, Liu Q, Wang J, et al: miR-302a inhibits metastasis and cetuximab resistance in colorectal cancer by targeting NFIB and CD44. Theranostics. 9:8409–8425. 2019. View Article : Google Scholar : PubMed/NCBI