首页|MicroRNA-375 Suppresses the Tumor Aggressive Phenotypes of Clear Cell Renal Cell Carcinomas through Regulating YWHAZ

MicroRNA-375 Suppresses the Tumor Aggressive Phenotypes of Clear Cell Renal Cell Carcinomas through Regulating YWHAZ

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  • 国家科技期刊平台
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Background:MicroRNAs (miRNAs) are key regulators during tumor initiation and progression.MicroRNA-375 (MiR-375) has been proven to play a tumor-suppressive role in various types of human malignancies;however,its biological role in clear cell renal cell carcinoma (ccRCC) remains unclear.The purpose of this study was to explore the biologic role as well as the underlying mechanism of miR-375 in ccRCC progression.Methods:Quantitative polymerase chain reaction (qPCR) was applied to test the expression of miR-375 in tissues and cell lines by t-test.Functional experiments were used to investigate the biological role of miR-375 utilizing a gain-of-function strategy.The target of miR-375 was investigated by bioinformatic analysis and further verified by luciferase reporter assay,qPCR,Western blotting,and functional experiments in vitro.Results:Our study demonstrated that miR-375 was significantly downregulated in ccRCC tissues (cancer vs.normal,0.804 ± 0.079 vs.1.784 ± 0.200,t =5.531 P ＜ 0.0001) and cell lines,and loss of miR-375 expression significantly associated with advanced Fuhrman nuclear grades (Grade III and IV vs.Grade Ⅰ and Ⅱ,1.000 ± 0.099 vs.1.731 ± 0.189,t =3.262 P =0.003).Functional studies demonstrated that miR-375 suppressed ccRCC cell proliferation,migration,and invasion (all P ＜ 0.05 in both 786-O and A498 cell lines).Multiple miRNA target prediction algorithms indicated the well-studied oncogene YWHAZ as a direct target ofmiR-375,which was further confirmed by the luciferase reporter assay,qPCR,and Western blotting.Moreover,restoration of YWHAZ could rescue the antiproliferation effect ofmiR-375.Conclusions:The data provide the solid evidence that miR-375 plays a tumor-suppressive role in ccRCC progression,partially through regulating YWHAZ.This study expands the antitumor profile ofmiR-375,and supports its role as a potential therapeutic target in ccRCC treatment.

Clear Cell Renal Cell CarcinomaMicroRNA-375ProliferationYWHAZ

Xiang Zhang、Nai-Dong Xing、Cheng-Jun Lai、Rui Liu、Wei Jiao、Jue Wang、Jie Song、Zhong-Hua Xu

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Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China

Teaching and Research Institute of Urology, School of Medicine, Shandong University, Jinan, Shandong 250012, China

Department of Urology, Qingyun People's Hospital, Dezhou, Shandong 253700, China

Department of the First Operation Room, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China

Central Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250012, China

Medicaid and Health Care Service Office, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China

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This work was supported by the grants from the National Natural Science Foundation of ChinaProvincial Natural Science Foundation of ShandongProvincial Natural Science Foundation of Shandong

81702521ZR2017PH019ZR2018BH018

2018

中华医学杂志(英文版)
中华医学会

中华医学杂志(英文版)

CSTPCDCSCDSCI
影响因子：0.838
ISSN：0366-6999
年,卷(期)：2018.131(16)
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