Inhibition of MIR4435-2HG on Invasion, Migration, and EMT of Gastric Carcinoma Cells by Mediating MiR-138-5p/Sox4 Axis

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Sep 17

PMID 34532282

Citations 15

Authors

Li-Fei Gao

Wei Li

Ya-Gang Liu

Cui Zhang

Wei-Na Gao

Liang Wang

Affiliations

Soon will be listed here.

Abstract

Background: The previous investigations have identified that long non-coding RNA (lncRNAs) act as crucial regulators in gastric carcinoma. However, the function of lncRNA MIR4435-2HG in the modulation of gastric carcinoma remains elusive. Here, we aimed to explore the role of MIR4435-2HG in gastric carcinoma.

Method: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were applied to select the differently expressed lncRNAs in gastric carcinoma. The qRT-PCR was applied to analyze MIR4435-2HG expression in carcinoma tissues and cell lines. The effect of MIR4435-2HG on proliferation, invasion, migration, and apoptosis of gastric carcinoma cells was detected by Cell Counting Kit-8 (CCK-8) assays, transwell assays, and flow cytometry . A subcutaneous tumor model was constructed to examine the tumor growth of gastric carcinoma cells after knocking out MIR4435-2HG. RNA immunoprecipitation and luciferase reporting assays were applied to evaluate the interaction of MIR4435-2HG, miR-138-5p, and Sox4.

Results: The bioinformatics analysis based on TCGA and GEO databases indicated that MIR4435-2HG was obviously elevated in gastric carcinoma samples. The qRT-PCR analysis revealed that MIR4435-2HG was upregulated in clinical gastric carcinoma tissues and cells. The high expression of MIR4435-2HG is associated with the poor survival rate of patients. The knockout of MIR4435-2HG could repress the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) and accelerate the apoptosis of gastric carcinoma cells. Moreover, the deletion of MIR4435-2HG was able to attenuate the tumor growth . Mechanically, we identified that MIR4435-2HG enhanced Sox4 expression by directly interacting with miR-138-5p as a competitive endogenous RNA (ceRNA) in gastric carcinoma cells, in which Sox4 was targeted by miR-138-5p.

Conclusion: MIR4435-2HG is elevated in gastric carcinoma cells and contributes to the growth, metastasis, and EMT of gastric carcinoma cells by targeting miR-138-5p/Sox4 axis. MIR4435-2HG may be applied as a potential therapeutic target in gastric carcinoma.

Citing Articles

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References

Wang H, Huo X, Yang X, He J, Cheng L, Wang N . STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4. Mol Cancer. 2017; 16(1):136. PMC: 5558651. DOI: 10.1186/s12943-017-0680-1. View

Guggenheim D, Shah M . Gastric cancer epidemiology and risk factors. J Surg Oncol. 2012; 107(3):230-6. DOI: 10.1002/jso.23262. View

Yu H, Wang C, Yuan Z, Chen G, Ye T, Yang B . LncRNA NEAT1 promotes the tumorigenesis of colorectal cancer by sponging miR-193a-3p. Cell Prolif. 2018; 52(1):e12526. PMC: 6430453. DOI: 10.1111/cpr.12526. View

Peng X, Liu G, Peng H, Chen A, Zha L, Wang Z . SOX4 contributes to TGF-β-induced epithelial-mesenchymal transition and stem cell characteristics of gastric cancer cells. Genes Dis. 2018; 5(1):49-61. PMC: 6147107. DOI: 10.1016/j.gendis.2017.12.005. View

Wang Y, Jiang F, Xiong Y, Cheng X, Qiu Z, Song R . LncRNA TTN-AS1 sponges miR-376a-3p to promote colorectal cancer progression via upregulating KLF15. Life Sci. 2019; 244:116936. DOI: 10.1016/j.lfs.2019.116936. View

Tian S, Guo X, Yu C, Sun C, Jiang J . miR-138-5p suppresses autophagy in pancreatic cancer by targeting SIRT1. Oncotarget. 2017; 8(7):11071-11082. PMC: 5355247. DOI: 10.18632/oncotarget.14360. View

Song Z, Wu Y, Yang J, Yang D, Fang X . Progress in the treatment of advanced gastric cancer. Tumour Biol. 2017; 39(7):1010428317714626. DOI: 10.1177/1010428317714626. View

Pang L, Cheng Y, Zou S, Song J . Long noncoding RNA SNHG7 contributes to cell proliferation, migration, invasion and epithelial to mesenchymal transition in non-small cell lung cancer by regulating miR-449a/TGIF2 axis. Thorac Cancer. 2019; 11(2):264-276. PMC: 6996990. DOI: 10.1111/1759-7714.13245. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

10.

Deng L, Chi Y, Liu L, Huang N, Wang L, Wu J . LINC00978 predicts poor prognosis in breast cancer patients. Sci Rep. 2016; 6:37936. PMC: 5126584. DOI: 10.1038/srep37936. View

11.

Luan X, Wang Y . LncRNA XLOC_006390 facilitates cervical cancer tumorigenesis and metastasis as a ceRNA against miR-331-3p and miR-338-3p. J Gynecol Oncol. 2018; 29(6):e95. PMC: 6189437. DOI: 10.3802/jgo.2018.29.e95. View

12.

. Issue Information-Declaration of Helsinki. J Bone Miner Res. 2018; 33(12):BM i-BM ii. DOI: 10.1002/jbmr.3277. View

13.

Zhang Y, Weinberg R . Epithelial-to-mesenchymal transition in cancer: complexity and opportunities. Front Med. 2018; 12(4):361-373. PMC: 6186394. DOI: 10.1007/s11684-018-0656-6. View

14.

Jiao J, Zhang S . Long non‑coding RNA MEG‑3 suppresses gastric carcinoma cell growth, invasion and migration via EMT regulation. Mol Med Rep. 2019; 20(3):2685-2693. PMC: 6691256. DOI: 10.3892/mmr.2019.10515. View

15.

Yang M, He X, Huang X, Wang J, He Y, Wei L . LncRNA MIR4435-2HG-mediated upregulation of TGF-β1 promotes migration and proliferation of nonsmall cell lung cancer cells. Environ Toxicol. 2019; 35(5):582-590. DOI: 10.1002/tox.22893. View

16.

Zhao L, Yu H, Yi S, Peng X, Su P, Xiao Z . The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer. Oncotarget. 2016; 7(29):45370-45384. PMC: 5216728. DOI: 10.18632/oncotarget.9659. View

17.

Mittal V . Epithelial Mesenchymal Transition in Tumor Metastasis. Annu Rev Pathol. 2018; 13:395-412. DOI: 10.1146/annurev-pathol-020117-043854. View

18.

Wang H, Wu M, Lu Y, He K, Cai X, Yu X . LncRNA MIR4435-2HG targets desmoplakin and promotes growth and metastasis of gastric cancer by activating Wnt/β-catenin signaling. Aging (Albany NY). 2019; 11(17):6657-6673. PMC: 6756883. DOI: 10.18632/aging.102164. View

19.

Chou C, Shrestha S, Yang C, Chang N, Lin Y, Liao K . miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions. Nucleic Acids Res. 2017; 46(D1):D296-D302. PMC: 5753222. DOI: 10.1093/nar/gkx1067. View

20.

Xia P, Xu X . Epithelial-mesenchymal transition and gastric cancer stem cell. Tumour Biol. 2017; 39(5):1010428317698373. DOI: 10.1177/1010428317698373. View