|Table of Contents|

Study on the mechanism of miR-4465 suppresses the proliferation,migration and invasion of gastric cancer cells by regulating the expression of EZH2

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2022 01
Page:
22-27
Research Field:
Publishing date:

Info

Title:
Study on the mechanism of miR-4465 suppresses the proliferation,migration and invasion of gastric cancer cells by regulating the expression of EZH2
Author(s):
ZHENG Huashan1CHEN Chenghui1CAI Qinping1LIN Xianke1LI He2
1.Donghu Surgery,the Second Affiliated Hospital of Hainan Medical College,Hainan Haikou 570100,China;2.General Surgery,the First Affiliated Hospital of Hainan Medical College,Hainan Haikou 570102,China.
Keywords:
miR-4465EZH2gastric cancerproliferationmigrationinvasion
PACS:
R735.2
DOI:
10.3969/j.issn.1672-4992.2022.01.005
Abstract:
Objective:To investigate the effect of miR-4465 on the proliferation,migration and invasion of gastric cancer cells by regulating the expression of EZH2.Methods:qRT-PCR was applied to detect the expression level of miR-4465 in gastric cancer tissues and cell lines.Overexpression of miR-4465 or silencing of EZH2 in MKN45 cells,and the proliferation,migration and invasion of MKN45 cells were detected by CCK-8 assay and Transwell assay.Western blotting was used to detect the expression of EZH2,E-cadherin,N-cadherin and Vimentin.The interaction between miR-4465 with EZH2 was verified by dual-luciferase reporter gene.Results:Compared with the adjacent tissues,the expression level of miR-4465 in gastric cancer tissues was decreased,and the expression level in gastric cancer cell lines(MCC-803,SGC7901,MKN45) was significantly lower than that in human immortalized gastric cell RGM-1,and the expression in MKN45 was lower than other cells.Overexpression of miR-4465 significantly inhibits the proliferation,migration,invasion and epithelial-mesenchymal transition of MKN45 cell.Dual-luciferase reporter gene result confirmed that miR-4465 was directly targeted with the 3'-UTR of EZH2.Further experiments showed that simultaneously silencing miR-4465 and EZH2 could restored the inhibitory effect of EZH2 silencing on the proliferation,invasion,migration and EMT of MKN45 cells.Conclusion:miR-4465 is inhibit the biological behavior of gastric cancer cells via targeting EZH2.miR-4465 may be a molecular target for the treatment of gastric cancer.

References:

[1] LIU XJ,LI SL,LI JS,et al.Long non-coding RNA ZEB1-AS1 is associated with poor prognosis in gastric cancer and promotes cancer cell metastasis[J].Eur Rev Med Pharmacol Sci,2018,22(9):2624-2630.
[2] GARZON R,MARCUCCI G,CROCE CM.Targeting microRNAs in cancer:rationale,strategies and challenges[J].Nat Rev Drug Discov,2010,9(10):775-789.
[3] BARTEL DP.MicroRNAs:genomics,biogenesis,mechanism,and function[J].Cell,2004,116(2):281-297.
[4] KONG YW,FERLAND-MCCOLLOUGH D,JACKSON TJ,et al.MicroRNAs in cancer management[J].The Lancet Oncology,2012,13(6):249-258.
[5] ZHANG K,ZHANG C,LIU L,et al.A key role of microRNA-29b in suppression of osteosarcoma cell proliferation and migration via modulation of VEGF[J].Int J Clin Exp Pathol,2014,7(9):5701-5708.
[6] JIANG XM,YU XN,LIU TT,et al.MicroRNA-19a-3p promotes tumor metastasis and chemoresistance through the PTEN/Akt pathway in hepatocellular carcinoma[J].Biomed Pharmacother,2018,105:1147-1154.
[7] HAN J,WANG F,LAN Y,et al.KIFC1 regulated by miR-532-3p promotes epithelial-to-mesenchymal transition and metastasis of hepatocellular carcinoma via gankyrin/AKT signaling[J].Oncogene,2018,38(3):406-420.
[8] VALK-LINGBEEK ME,BRUGGEMAN SW,VAN LOHUIZEN M.Stem cells and cancer,the polycomb connection[J].Cell,2004,118(4):409-418.
[9] MAHMOUDI T,VERRIJZER CP.Chromatin silencing and activation by Polycomb and trithorax group proteins[J].Oncogene,2001,20(24):3055-3066.
[10] SUN J,TIAN X,LU SQ,et al.MicroRNA-4465 suppresses tumor proliferation and metastasis in non-small cell lung cancer by directly targeting the oncogene EZH2[J].Biomed Pharmacother,2017,96:1358-1362.
[11] CHEN WQ,ZHENG RS,BAADE PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[12] KARIMI P,ISLAMI F,ANANDASABAPATHY S,et al.Gastric cancer:descriptive epidemiology,risk factors,screening,and prevention[J].Cancer Epidemiol Biomarkers Prev,2014,23(5):700-713.
[13] AL-HAIDARI AA,SYK I,THORLACIUS H.MiR-155-5p positively regulates CCL17-induced colon cancer cell migration by targeting RhoA[J].Oncotarget,2017,8(9):14887-14896.
[14] CHEN D,DANG BL,HUANG JZ,et al.MiR-373 drives the epithelial-to-mesenchymal transition and metastasis via the miR-373-TXNIP-HIF1alpha-TWIST signaling axis in breast cancer[J].Oncotarget,2015,6(32):32701-32712.
[15] FU X,ZHANG W,SU Y,et al.MicroRNA-103 suppresses tumor cell proliferation by targeting PDCD10 in prostate cancer[J].Prostate,2016,76(6):543-551.
[16] ZHAO X,JI Z,XIE Y,et al.MicroRNA-154 as a prognostic factor in bladder cancer inhibits cellular malignancy by targeting RSF1 and RUNX2[J].Oncol Rep,2017,38(5):2727-2734.
[17] LIN C,LI Z,CHEN P,et al.Oncogene miR-154-5p regulates cellular function and acts as a molecular marker with poor prognosis in renal cell carcinoma[J].Life Sci,2018,15(209):481-489.
[18] ZHAO L,FENG X,SONG X,et al.miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4[J].Oncol Rep,2016,36(2):1007-1015.
[19] ZHAO S,GAO X,ZANG S,et al.MicroRNA-383-5p acts as a prognostic marker and inhibitor of cell proliferation in lung adenocarcinoma by cancerous inhibitor of protein phosphatase 2A[J].Oncol Lett,2017,14(3):3573-3579.
[20] TAO Z,FENG C,MAO C,et al.MiR-4465 directly targets PTEN to inhibit AKT/mTOR pathway-mediated autophagy[J].Cell Stress Chaperones,2018,24(1):105-113.
[21] BENETATOS L,VOULGARIS E,VARTHOLOMATOS G,et al.Non-coding RNAs and EZH2 interactions in cancer:long and short tales from the transcriptome[J].Int J Cancer,2013,133(2):267-274.
[22] KIM KH,ROBERTS CW.Targeting EZH2 in cancer[J].Nat Med,2016,22(2):128-134.
[23] LIU F,HE Y,SHU R,et al.MicroRNA-1297 regulates hepatocellular carcinoma cell proliferation and apoptosis by targeting EZH2[J].Int J Clin Exp Pathol,2015,8(5):4972-4980.
[24] CHEN DL,ZHANG DS,LU YX,et al.MicroRNA-217 inhibits tumor progression and metastasis by downregulating EZH2 and predicts favorable prognosis in gastric cancer[J].Oncotarget,2015,6(13):10868-10879.

Memo

Memo:
海南省重点研发计划(编号:812201)
Last Update: 2021-12-02