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miR-146a-5p通过调控SOX5对三阴性乳腺癌增殖和转移的影响

Effect of miR-146a-5p on proliferation and metastasis of triple-negative breast cancer via regulation of SOX5.

作者信息

Si Chengshuai, Yu Qiao, Yao Yufeng

机构信息

Department of General Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research and Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu 210009, P.R. China.

出版信息

Exp Ther Med. 2018 May;15(5):4515-4521. doi: 10.3892/etm.2018.5945. Epub 2018 Mar 9.

DOI:10.3892/etm.2018.5945
PMID:29731835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5920859/
Abstract

MicroRNA (miR)-146a-5p functions as a tumor suppressor in various types of cancer. However, the role of miR-146a-5p in the development of triple-negative breast cancer (TNBC) is unclear. The present study aimed to investigate the role of miR-146a-5p in TNBC. The expression level of miR-146a-5p in TNBC tissues and cell lines was initially detected using reverse transcription-quantitative polymerase chain reaction. To predict the target gene of miR-146a-5p, TargetScan software was used and a dual luciferase assay was performed to verify the prediction. Furthermore, in order to explore the role of miR-146a-5p in TNBC, miR-146a-5p was overexpressed in TNBC cells using miR-146a-5p mimics. An MTT assay was performed to detect cell proliferation, and a Transwell assay was conducted to determine cell migration and invasion. Furthermore, western blotting was performed to measure associated protein expression. It was revealed that miR-146a-5p was downregulated in TNBC tissues and cell lines. SOX5 was indicated to be a target gene of miR-146a-5p and was upregulated in TNBC cells. Additionally, miR-146a-5p could inhibit TNBC cell proliferation, migration and invasion, repress the expression of mesenchymal markers (N-cadherin, vimentin and fibronectin) and increase epithelial marker (E-cadherin) expression. Furthermore, SOX5 overexpression eliminated the effects of miR-146a-5p mimics on TNBC cells. In conclusion, the data of the present study indicated that miR-146a-5p inhibits the proliferation and metastasis of TNBC cells by regulating SOX5.

摘要

微小RNA(miR)-146a-5p在多种类型癌症中发挥肿瘤抑制作用。然而,miR-146a-5p在三阴性乳腺癌(TNBC)发生发展中的作用尚不清楚。本研究旨在探讨miR-146a-5p在TNBC中的作用。首先采用逆转录-定量聚合酶链反应检测TNBC组织和细胞系中miR-146a-5p的表达水平。为预测miR-146a-5p的靶基因,使用TargetScan软件并进行双荧光素酶报告基因检测以验证预测结果。此外,为探究miR-146a-5p在TNBC中的作用,使用miR-146a-5p模拟物在TNBC细胞中过表达miR-146a-5p。进行MTT检测以检测细胞增殖,并进行Transwell检测以确定细胞迁移和侵袭能力。此外,进行蛋白质印迹法检测相关蛋白表达。结果显示,miR-146a-5p在TNBC组织和细胞系中表达下调。SOX5被表明是miR-146a-5p的靶基因且在TNBC细胞中上调。此外,miR-146a-5p可抑制TNBC细胞的增殖、迁移和侵袭,抑制间充质标志物(N-钙黏蛋白、波形蛋白和纤连蛋白)的表达并增加上皮标志物(E-钙黏蛋白)的表达。此外,SOX5过表达消除了miR-146a-5p模拟物对TNBC细胞的影响。总之,本研究数据表明miR-146a-5p通过调控SOX5抑制TNBC细胞的增殖和转移。

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