MicroRNA‑383‑5p inhibits the proliferation and promotes the apoptosis of gastric cancer cells by targeting cancerous inhibitor of PP2A

Li,Xinxin; Yuan,Jinpeng; Cao,Qiangjian; Xie,Aosi; Chen,Juntian

doi:10.3892/ijmm.2020.4603

MicroRNA‑383‑5p inhibits the proliferation and promotes the apoptosis of gastric cancer cells by targeting cancerous inhibitor of PP2A

Authors:
- Xinxin Li
- Jinpeng Yuan
- Qiangjian Cao
- Aosi Xie
- Juntian Chen
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Affiliations: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
Published online on: May 12, 2020 https://doi.org/10.3892/ijmm.2020.4603
Pages: 397-405

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Abstract

The aberrant expression of microRNA (miRNAor miR)‑383‑5p has been found in numerous types of cancer. However, the function of miR‑383‑5p in gastric cancer (GC) remains elusive and requires further investigation. In the present study, the level of miR‑383‑5p and cancerous inhibitor of PP2A (CIP2A) in GC cell lines was determined by reverse transcription‑quantitative PCR analysis. GC cell proliferation, apoptosis and cell cycle distribution were determined by the MTT assay and flow cytometry, respectively. The mRNA target of miR‑383‑5p was identified by dual luciferase activity assay. It was observed that the expression of miR‑383‑5p was lower and that of CIP2A was higher in GC cells compared with the GES‑1 normal human gastric epithelial cell line. Transfectoin with miR‑383‑5p mimic significantly inhibited GC cell proliferation, while it promoted cell apoptosis and G0/G1 arrest by targeting CIP2A. Taken together, the findings of the present study demonstrate that miR‑383‑5p inhibits GC cell proliferation and promotes apoptosis and G0/G1 arrest by targeting CIP2A, indicating that targeting miR‑383‑5p may hold promise as a future therapeutic strategy for patients with GC.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Yeh JM, Kuntz KM, Ezzati M, Hur C, Kong CY and Goldie SJ: Development of an empirically calibrated model of gastric cancer in two high-risk countries. Cancer Epidemiol Biomarkers Prev. 17:1179–1187. 2008. View Article : Google Scholar : PubMed/NCBI
3	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
4	Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Rådmark O, Kim S and Kim VN: The nuclear RNase III Drosha initiates microRNA processing. Nature. 425:415–419. 2003. View Article : Google Scholar : PubMed/NCBI
5	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
6	Ma L, Teruya-Feldstein J and Weinberg RA: Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 449:682–688. 2007. View Article : Google Scholar : PubMed/NCBI
7	Zhao H, Guo M, Zhao G, Ma Q, Ma B, Qiu X and Fan Q: miR-183 inhibits the metastasis of osteosarcoma via downregulation of the expression of Ezrin in F5M2 cells. Int J Mol Med. 30:1013–1020. 2012. View Article : Google Scholar : PubMed/NCBI
8	Schaefer A, Jung M, Mollenkopf HJ, Wagner I, Stephan C, Jentzmik F, Miller K, Lein M, Kristiansen G and Jung K: Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer. 126:1166–1176. 2010.
9	Wang J, Zhou Y, Fei X, Chen X and Chen Y: Biostatistics mining associated method identifies AKR1B10 enhancing hepatocellular carcinoma cell growth and degenerated by miR-383-5p. Sci Rep. 8:110942018. View Article : Google Scholar : PubMed/NCBI
10	Zhang J, Kong X, Shi Q and Zhao B: MicroRNA-383-5p acts as a potential prognostic biomarker and an inhibitor of tumor cell proliferation, migration, and invasion in breast cancer. Cancer Biomark. 27:423–432. 2020. View Article : Google Scholar : PubMed/NCBI
11	Hu Y, Ma Y, Liu J, Cai Y, Zhang M and Fang X: LINC01128 expedites cervical cancer progression by regulating miR-383-5p/SFN axis. BMC Cancer. 19:11572019. View Article : Google Scholar : PubMed/NCBI
12	Shao B, Fu X, Li X, Li Y and Gan N: RP11-284F21.9 promotes oral squamous cell carcinoma development via the miR-383-5p/MAL2 axis. J Oral Pathol Med. 49:21–29. 2020. View Article : Google Scholar
13	Wei C and Gao JJ: Downregulated miR-383-5p contributes to the proliferation and migration of gastric cancer cells and is associated with poor prognosis. Peer J. 7:e78822019. View Article : Google Scholar : PubMed/NCBI
14	Xu G, Li N, Zhang Y, Zhang J, Xu R and Wu Y: MicroRNA-383-5p inhibits the progression of gastric carcinoma via targeting HDAC9 expression. Braz J Med Biol Res. 52:e83412019. View Article : Google Scholar : PubMed/NCBI
15	Soo Hoo L, Zhang JY and Chan EK: Cloning and characterization of a novel 90 kDa 'companion' auto-antigen of p62 overexpressed in cancer. Oncogene. 21:5006–5015. 2002. View Article : Google Scholar : PubMed/NCBI
16	Dong QZ, Wang Y, Dong XJ, Li ZX, Tang ZP, Cui QZ and Wang EH: CIP2A is overexpressed in non-small cell lung cancer and correlates with poor prognosis. Ann Surg Oncol. 18:857–865. 2011. View Article : Google Scholar
17	Huang LP, Adelson ME, Mordechai E and Trama JP: CIP2A expression is elevated in cervical cancer. Cancer Biomark. 8:309–317. 2010. View Article : Google Scholar : PubMed/NCBI
18	Vaarala MH, Väisänen MR and Ristimäki A: CIP2A expression is increased in prostate cancer. J Exp Clin Cancer Res. 29:1362010. View Article : Google Scholar : PubMed/NCBI
19	Li W, Ge Z, Liu C, Liu Z, Björkholm M, Jia J and Xu D: CIP2A is overexpressed in gastric cancer and its depletion leads to impaired clonogenicity, senescence, or differentiation of tumor cells. Clin Cancer Res. 14:3722–3728. 2008. View Article : Google Scholar : PubMed/NCBI
20	Zhao S, Gao X, Zang S, Li Y, Feng X and Yuan X: MicroRNA-383-5p acts as a prognostic marker and inhibitor of cell proliferation in lungadenocarcinoma by cancerous inhibitor of protein phosphatase 2A. Oncol Lett. 14:3573–3579. 2017. 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
22	Liu YW, Xia R, Lu K, Xie M, Yang F, Sun M, De W, Wang C and Ji G: LincRNAFEZF1-AS1 represses p21 expression to promote gastric cancer proliferation through LSD1-mediated H3K4me2 demethylation. Mol Cancer. 16:392017. View Article : Google Scholar : PubMed/NCBI
23	Wang S, Wang X, Gao Y, Peng Y, Dong N, Xie Q, Zhang X, Wu Y, Li M and Li JL: RN181 is a tumour suppressor in gastric cancer by regulation of the ERK/MAPK-cyclin D1/CDK4 pathway. J Pathol. 248:204–216. 2019. View Article : Google Scholar : PubMed/NCBI
24	Korsmeyer SJ, Shutter JR, Veis DJ, Merry DE and Oltvai ZN: Bcl-2/Bax: A rheostat that regulates an anti-oxidant pathway and cell death. Semin Cancer Biol. 4:327–332. 1993.PubMed/NCBI
25	Chen L, Guan H, Gu C, Cao Y, Shao J and Wang F: miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL. Tumour Biol. 37:2497–2507. 2016. View Article : Google Scholar
26	Han S, Cao C, Tang T, Lu C, Xu J, Wang S, Xue L, Zhang X and Li M: ROBO3 promotes growth and metastasis of pancreatic carcinoma. Cancer Lett. 366:61–70. 2015. View Article : Google Scholar : PubMed/NCBI
27	He Z, Cen D, Luo X, Li D, Li P, Liang L and Meng Z: Downregulation of miR-383 promotes glioma cell invasion by targeting insulin-like growth factor 1 receptor. Med Oncol. 30:5572013. View Article : Google Scholar : PubMed/NCBI
28	Chen S, Wu J, Jiao K, Wu Q, Ma J, Chen D, Kang J and Zhao G, Shi Y, Fan D and Zhao G: MicroRNA-495-3p inhibits multidrug resistance by modulating autophagy through GRP78/mTOR axis in gastric cancer. Cell Death Dis. 9:10702018. View Article : Google Scholar : PubMed/NCBI
29	Zhang F, Li K, Pan M, Li W, Wu J, Li M, Zhao L and Wang H: miR-589 promotes gastric cancer aggressiveness by a LIFR-PI3K/AKT-c-Jun regulatory feedback loop. J Exp Clin Cancer Res. 37:1522018. View Article : Google Scholar : PubMed/NCBI
30	Jiang J, Xie C, Liu Y, Shi Q and Chen Y: Up-regulation of miR-83-5p suppresses proliferation and enhances chemosensitivity in ovarian cancer cells by targeting TRIM27. Biomed Pharmacother. 109:595–601. 2019. View Article : Google Scholar
31	Chao TT, Wang CY, Lai CC, Chen YL, Tsai YT, Chen PT, Lin HI, Huang YC, Shiau CW, Yu CJ and Chen KF: TD-19, an erlotinib derivative, induces epidermal growth factor receptor wild-type nonsmall-cell lung cancer apoptosis through CIP2A-mediated pathway. J Pharmacol Exp Ther. 351:352–358. 2014. View Article : Google Scholar : PubMed/NCBI
32	Lei N, Peng B and Zhang JY: CIP2A regulates cell proliferation via the AKT signaling pathway in human lung cancer. Oncol Rep. 32:1689–1694. 2014. View Article : Google Scholar : PubMed/NCBI
33	Zhai H, Fesler A, Schee K, Fodstad O, Flatmark K and Ju J: Clinical significance of long intergenic noncoding RNA-p21 in colorectal cancer. Clin Colorectal Cancer. 12:261–266. 2013. View Article : Google Scholar : PubMed/NCBI
34	Pozner A, Terooatea TW and Buck-Koehntop BA: Cell-specific kaiso (ZBTB33) regulation of cell cycle through cyclin D1 and cyclin E1. J Biol Chem. 291:24538–24550. 2016. View Article : Google Scholar : PubMed/NCBI
35	Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T and Tanaka N: Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science. 288:1053–1058. 2000. View Article : Google Scholar : PubMed/NCBI
36	LeBlanc H, Lawrence D, Varfolomeev E, Totpal K, Morlan J, Schow P, Fong S, Schwall R, Sinicropi D and Ashkenazi A: Tumor-cell resistance to death receptor-induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat Med. 8:274–281. 2002. View Article : Google Scholar : PubMed/NCBI