Objective:MicroRNA(miRNA/miR)-633 is dysregulated in several types of cancers and is involved in tumorigenesis.However,the function and role of this miRNA in gastric cancer(GC)are not fully understood.The aim of the present study was to evaluate miR-633 expression in GC cell lines and in GC tissue vs.adjacent normal tissue,and to determine its association with clinicopathological data.This work was extended to investigate the effects of miR-633 overexpression on tumor cells in vitro.Methods:Reverse transcription-quantitative PCR(RT-qPCR)was used to detect and compare the expression level of miR-633 in GC cells,as well as in GC and normal adjacent tissue samples.The clinical significance of miR-633 was also analyzed.MiR-633 lentivirus(LV-miR-633)and negative control lentivirus(LV-NC)were generated and used to transduce SGC-7901 and HGC-27 GC cells in order to analyze the effect of miR-633 on their phenotype.The effects of miR-633 overexpression on GC cell proliferation,apoptosis,migration and invasion were investigated.The target gene of miR-633 was predicted,then confirmed using a dual luciferase reporter gene assay,RT-qPCR and Western blotting.Results:MiR-633 was significantly downregulated in GC cell lines,as well as in GC tissue compared with adjacent normal tissue.Moreover,miR-633 expression was associated with the tumor/node/metastasis(TNM)stage,invasion depth,Borrmann classification and lymph node metastasis(P＜0.05).Compared with the LV-NC group,transduction with LV-miR-633 reduced the proliferation,the number of clones,the wound healing rate,the number of invading cells and the number of cells in the G1 phase of the cell cycle(P＜0.01).LV-miR-633 also increased the apoptosis rate(P＜0.01).The expression level of mitogen-activated protein kinase(MAPK)1,high-mobility group box 3(HMGB3),claudin 1(CLDN1)and MAPK 13 were downregulated in LV-miR-633-transduced cells(P＜0.01).The dual luciferase reporter assay confirmed that the 3'-untranslated region of MAPK 1 was the target site of miR-633(P＜0.01).Conclusion:MiR-633 acts as a tumor suppressor in GC,and its expression level is associated with TNM stage,invasion depth,Borrmann type and lymph node metastasis.Overexpression of miR-633 inhibits the proliferation and migration of GC cells and induces apoptosis and cell cycle arrest at the in G1 phase.In addition,miR-633 negatively regulates the expression of MAPK1,HMGB3,CLDN1 and MAPK13 and directly targets MAPK1.

Hai-long LI;Yao-hui SONG;Zheng-ping DU;Yong-hua HU;Zhuan-xiong WANG;Xi CHEN;Xing-mei LU;Ying-xia CHEN;Yong-qiang DUAN;Xiang-dong ZHU

Department of Geriatrics,Affiliated Hospital of Gansu University of Traditional Chinese Medicine,Lanzhou 730000,China;Department of Internal Medicine,The First Clinical Medical College,Gansu University of Chinese Medicine,Lanzhou 730000,China;Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and The Prevention and Treatment with Traditional Chinese Medicine in Gansu Colleges and Universities,Gansu University of Chinese Medicine,Lanzhou 730000,China;School of Basic Medicine,Gansu Vocational College of Health,Lanzhou 730300,China;College of Traditional Chinese Medicine,Ningxia Medical University,Yinchuan 750004,China

当代医学科学(英文)

[1]Hai-long LI;Yao-hui SONG;Zheng-ping DU;Yong-hua HU;Zhuan-xiong WANG;Xi CHEN;Xing-mei LU;Ying-xia CHEN;Yong-qiang DUAN;Xiang-dong ZHU-.Overexpression of MiR-633 Suppresses the Tumorigenicity of Gastric Cancer Cells and Induces Apoptosis by Targeting MAPK1)[J].当代医学科学(英文),2022(05):1033-1045

Tumorigenicity,HMGB3,MAPK13

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