lncRNA MALAT1 promotes cell proliferation and invasion by regulating the miR‑101/EZH2 axis in oral squamous cell carcinoma

Xiao,Lei; Wang,Weiping; Zhao,Jingjing; Xu,Hongyan; Li,Shaozhen; Yang,Xiuhua

doi:10.3892/ol.2020.12024

lncRNA MALAT1 promotes cell proliferation and invasion by regulating the miR‑101/EZH2 axis in oral squamous cell carcinoma

Authors:
- Lei Xiao
- Weiping Wang
- Jingjing Zhao
- Hongyan Xu
- Shaozhen Li
- Xiuhua Yang
View Affiliations

Affiliations: Department of Stomatology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China, Department of Stomatology, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China, Department of Surgery, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China, Department of Stomatology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710000, P.R. China, Department of Imaging, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China, Department of Pharmacy, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China
Published online on: August 26, 2020 https://doi.org/10.3892/ol.2020.12024
Article Number: 164
Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity. Emerging evidence indicates that long non‑coding (lnc)RNAs play a key role in the cellular processes of tumor cells, including glycolysis, growth and movement. Here, the purpose of this study was to explore the biological functions and potential mechanism of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in OSCC. OSCC tissues and adjacent matched paraneoplastic normal tissues were collected from 20 OSCC patients. The expression of MALAT1 and miR‑101 in OSCC tissues and cell lines (HSC3, SCC9, SCC15 and SCC25) were determined by real‑time‑polymerase chain reaction (qPCR). Caspase‑3, xaspase‑8 and EZH2 protein levels were determined by western blot analysis. MALAT1‑mediated miRNAs were verified by bioinformatics analysis of StarBase and Luciferase reporter assay. Cell Counting Kit‑8 (CCK‑8) and Transwell assays were used for investigating MALAT1 effect on cell proliferation and invasion in the OSCC cells. qPCR analysis indicated that MALAT1 expression was obviously increased, and miR‑101 was decreased in the OSCC tissues and cell lines. Functional studies revealed that overexpression of MALAT1 promoted OSCC cell proliferation and invasion. Further experiments revealed that miR‑101 was a target of MALAT1 and that the miR‑101 inhibitor abolished the effect of MALAT1 on OSCC cell proliferation and invasion. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) acted as a downstream effecter of MALAT1 in the OSCC cells. Collectively, these findings revealed that upregulation of MALAT1 facilitated OSCC proliferation and invasion by targeting the miR‑101/EZH2 axis.

View Figures

View References

1	Choi S and Myers JN: Molecular pathogenesis of oral squamous cell carcinoma: Implications for therapy. J Dent Res. 87:14–32. 2008. View Article : Google Scholar : PubMed/NCBI
2	Johnson NW, Jayasekara P and Amarasinghe AA: Squamous cell carcinoma and precursor lesions of the oral cavity: Epidemiology and aetiology. Periodontol 2000. 57:19–37. 2011. View Article : Google Scholar : PubMed/NCBI
3	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
4	Sinevici N and O'sullivan J: Oral cancer: Deregulated molecular events and their use as biomarkers. Oral Oncol. 61:12–18. 2016. View Article : Google Scholar : PubMed/NCBI
5	Wang S, Hui Y, Li X and Jia Q: Silencing of lncRNA CCDC26 restrains the growth and migration of glioma cells in vitro and in vivo via targeting miR-203. Oncol Res. 26:1143–1154. 2018. View Article : Google Scholar : PubMed/NCBI
6	Zhang JJ, Wang DD, Du CX and Wang Y: Long noncoding RNA ANRIL promotes cervical cancer development by acting as a sponge of miR-186. Oncol Res. 26:345–352. 2018. View Article : Google Scholar : PubMed/NCBI
7	Gao YL, Zhao ZS, Zhang MY, Han LJ, Dong YJ and Xu B: Long noncoding RNA PVT1 facilitates cervical cancer progression via negative regulating of miR-424. Oncol Res. 25:1391–1398. 2017. View Article : Google Scholar : PubMed/NCBI
8	Hua F, Li CH, Chen XG and Liu XP: Long noncoding RNA CCAT2 knockdown suppresses tumorous progression by sponging miR-424 in epithelial ovarian cancer. Oncol Res. 26:241–247. 2018. View Article : Google Scholar : PubMed/NCBI
9	Ji P, Diederichs S, Wang W, Böing S, Metzger R, Schneider PM, Tidow N, Brandt B, Buerger H, Bulk E, et al: MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 22:8031–8041. 2003. View Article : Google Scholar : PubMed/NCBI
10	Zheng HT, Shi DB, Wang YW, Li XX, Xu Y, Tripathi P, Gu WL, Cai GX and Cai SJ: High expression of lncRNA MALAT1 suggests a biomarker of poor prognosis in colorectal cancer. Int J Clin Exp Pathol. 7:3174–3181. 2014.PubMed/NCBI
11	Croce CM: Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 10:704–714. 2009. View Article : Google Scholar : PubMed/NCBI
12	Wu B, Lei D, Wang L, Yang X, Jia S, Yang Z, Shan C, Yang X, Zhang C and Lu B: MiRNA-101 inhibits oral squamous-cell carcinoma growth and metastasis by targeting zinc finger E-box binding homeobox 1. Am J Cancer Res. 6:1396–1407. 2016.PubMed/NCBI
13	Jiang M, Xu B, Li X, Shang Y, Chu Y, Wang W, Chen D, Wu N, Hu S, Zhang S, et al: O-GlcNAcylation promotes colorectal cancer metastasis via the miR-101-O-GlcNAc/EZH2 regulatory feedback circuit. Oncogene. 38:301–316. 2019. View Article : Google Scholar : PubMed/NCBI
14	Chen L, Jia J, Zang Y, Li J and Wan B: MicroRNA-101 regulates autophagy, proliferation and apoptosis via targeting EZH2 in laryngeal squamous cell carcinoma. Neoplasma. 66:507–515. 2019. View Article : Google Scholar : PubMed/NCBI
15	Jin Q, He W, Chen L, Yang Y, Shi K and You Z: MicroRNA-101-3p inhibits proliferation in retinoblastoma cells by targeting EZH2 and HDAC9. Exp Ther Med. 16:1663–1670. 2018.PubMed/NCBI
16	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
17	Bertone P, Stolc V, Royce TE, Rozowsky JS, Urban AE, Zhu X, Rinn JL, Tongprasit W, Samanta M, Weissman S, et al: Global identification of human transcribed sequences with genome tiling arrays. Science. 306:2242–2246. 2004. View Article : Google Scholar : PubMed/NCBI
18	Zhang H, Chen Z, Wang X, Huang Z, He Z and Chen Y: Long non-coding RNA: A new player in cancer. J Hematol Oncol. 6:372013. View Article : Google Scholar : PubMed/NCBI
19	Tang D, Yang Z, Long F, Luo L, Yang B, Zhu R, Sang X and Cao G: Inhibition of MALAT1 reduces tumor growth and metastasis and promotes drug sensitivity in colorectal cancer. Cell Signal. 57:21–28. 2019. View Article : Google Scholar : PubMed/NCBI
20	Yao Y, Chen X, Lu S, Zhou C, Xu G, Yan Z, Yang J, Yu T, Chen W, Qian Y, et al: Circulating long noncoding RNAs as biomarkers for predicting head and neck squamous cell carcinoma. Cell Physiol Biochem. 50:1429–1440. 2018. View Article : Google Scholar : PubMed/NCBI
21	Zhuo M, Yuan C, Han T, Cui J, Jiao F and Wang L: A novel feedback loop between high MALAT-1 and low miR-200c-3p promotes cell migration and invasion in pancreatic ductal adenocarcinoma and is predictive of poor prognosis. BMC Cancer. 18:10322018. View Article : Google Scholar : PubMed/NCBI
22	Xu Y, Zhang X, Hu X, Zhou W, Zhang P, Zhang J, Yang S and Liu Y: The effects of lncRNA MALAT1 on proliferation, invasion and migration in colorectal cancer through regulating SOX9. Mol Med. 24:522018. View Article : Google Scholar : PubMed/NCBI
23	Pan Y, Tong S, Cui R, Fan J, Liu C, Lin Y, Tang J, Xie H, Lin P, Zheng T and Yu X: Long non-coding MALAT1 functions as a competing endogenous RNA to regulate vimentin expression by sponging miR-30a-5p in hepatocellular carcinoma. Cell Physiol Biochem. 50:108–120. 2018. View Article : Google Scholar : PubMed/NCBI
24	Huang XJ, Xia Y, He GF, Zheng LL, Cai YP, Yin Y and Wu Q: MALAT1 promotes angiogenesis of breast cancer. Oncol Rep. 40:2683–2689. 2018.PubMed/NCBI
25	Zhu K, Ren Q and Zhao Y: lncRNA MALAT1 overexpression promotes proliferation, migration and invasion of gastric cancer by activating the PI3K/AKT pathway. Oncol Lett. 17:5335–5342. 2019.PubMed/NCBI
26	Lin N, Yao Z, Xu M, Chen J, Lu Y, Yuan L, Zhou S, Zou X and Xu R: Long noncoding RNA MALAT1 potentiates growth and inhibits senescence by antagonizing ABI3BP in gallbladder cancer cells. J Exp Clin Cancer Res. 38:2442019. View Article : Google Scholar : PubMed/NCBI
27	Stone JK, Kim JH, Vukadin L, Richard A, Giannini HK, Lim SS, Tan M and Ahn EE: Hypoxia induces cancer cell-specific chromatin interactions and increases MALAT1 expression in breast cancer cells. J Biol Chem. 294:11213–11224. 2019. View Article : Google Scholar : PubMed/NCBI
28	Zhou X, Liu S, Cai G, Kong L, Zhang T, Ren Y, Wu Y, Mei M, Zhang L and Wang X: Long Non-coding RNA MALAT1 promotes tumor growth and metastasis by inducing epithelial-mesenchymal transition in oral squamous cell carcinoma. Sci Rep. 5:159722015. View Article : Google Scholar : PubMed/NCBI
29	Chang SM and Hu WW: Long non-coding RNA MALAT1 promotes oral squamous cell carcinoma development via microRNA-125b/STAT3 axis. J Cell Physiol. 233:3384–3396. 2018. View Article : Google Scholar : PubMed/NCBI
30	Pan L, Chen H, Bai Y, Wang Q and Chen L: Long non-coding RNA CASC2 serves as a ceRNA of microRNA-21 to promote PDCD4 expression in oral squamous cell carcinoma. Onco Targets Ther. 12:3377–3385. 2019. View Article : Google Scholar : PubMed/NCBI
31	Zhang P, Liu Y, Li C, Zhang L, Liu Q and Jiang T: LncRNA PAPAS promotes oral squamous cell carcinoma by upregulating transforming growth factor-β1. J Cell Biochem. 120:16120–16127. 2019. View Article : Google Scholar : PubMed/NCBI
32	Zhang C, Bao C, Zhang X, Lin X, Pan D and Chen Y: Knockdown of lncRNA LEF1-AS1 inhibited the progression of oral squamous cell carcinoma (OSCC) via Hippo signaling pathway. Cancer Biol Ther. 20:1213–1222. 2019. View Article : Google Scholar : PubMed/NCBI
33	Yu Q, Xiang L, Chen Z, Liu X, Ou H, Zhou J and Yang D: MALAT1 functions as a competing endogenous RNA to regulate SMAD5 expression by acting as a sponge for miR-142-3p in hepatocellular carcinoma. Cell Biosci. 9:392019. View Article : Google Scholar : PubMed/NCBI
34	Wang Y, Guo W, Li Z, Wu Y, Jing C, Ren Y, Zhao M, Kong L, Zhang C, Dong J, et al: Role of the EZH2/miR-200 axis in STAT3-mediated OSCC invasion. Int J Oncol. 52:1149–1164. 2018.PubMed/NCBI
35	Hong Y, He H, Sui W, Zhang J, Zhang S and Yang D: Long non-coding RNA H1 promotes cell proliferation and invasion by acting as a ceRNA of miR-138 and releasing EZH2 in oral squamous cell carcinoma. Int J Oncol. 52:901–912. 2018.PubMed/NCBI
36	Zhang D, Ni Z, Xu X and Xiao J: miR-32 functions as a tumor suppressor and directly targets EZH2 in human oral squamous cell carcinoma. Med Sci Monit. 20:2527–2535. 2014. View Article : Google Scholar : PubMed/NCBI