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微小RNA-21通过靶向磷酸酶及张力蛋白同源物(PTEN)促进三阴性乳腺癌细胞的增殖和侵袭。

miRNA-21 promotes proliferation and invasion of triple-negative breast cancer cells through targeting PTEN.

作者信息

Fang Hong, Xie Jiping, Zhang Min, Zhao Ziwei, Wan Yi, Yao Yongqiang

机构信息

Breast and Thyroid Surgery Ward III, The Affiliated Zhongshan Hospital of Dalian University Dalian 116001, Liaoning Province, China.

出版信息

Am J Transl Res. 2017 Mar 15;9(3):953-961. eCollection 2017.

Abstract

MicroRNAs (miRNAs) are small single-stranded RNAs that bind to the 3'UTR of the mRNAs of target genes. They can target multiple genes and regulate translation or degradation of the mRNA. miRNAs target genes in a tissue-specific manner, and the role of a particular miRNA varies according to tumor origin or even subtype within the same cancer. This study evaluated the effect of miR-21 expression in triple-negative breast cancer (TNBC) tissues and MDA-MB-468, a cell line derived from TNBC tissues. miR-21 was consistently upregulated in TNBC and MDA-MB-468 cells compared to normal tissues. Inhibition of miR-21 by miR-21 antisense oligonucleotides decreased the proliferation, viability, and invasiveness of MDA-MB-468 cells and enhanced apoptosis. Furthermore, we confirmed that PTEN was downregulated by miR-21 in MDA-MB-468 cells. The results indicated that PTEN may mediate the oncogenic properties of miR-21 in TNBC. In summary, miR-21 was upregulated in TNBC tissues and cells, and promoted the proliferation and invasion of MDA-MB-468 cells, but negatively regulated the expression of PTEN protein. Inhibition of miR-21 or overexpression of PTEN protein could be promising strategies for the treatment of patients with TNBC.

摘要

微小RNA(miRNA)是一类小的单链RNA,可与靶基因mRNA的3'非翻译区(3'UTR)结合。它们可以靶向多个基因,并调节mRNA的翻译或降解。miRNA以组织特异性方式靶向基因,并且特定miRNA的作用会因肿瘤起源甚至同一癌症内的亚型而异。本研究评估了miR-21在三阴性乳腺癌(TNBC)组织以及源自TNBC组织的细胞系MDA-MB-468中的表达影响。与正常组织相比,miR-21在TNBC和MDA-MB-468细胞中持续上调。用miR-21反义寡核苷酸抑制miR-21可降低MDA-MB-468细胞的增殖、活力和侵袭能力,并增强细胞凋亡。此外,我们证实miR-21在MDA-MB-468细胞中下调了PTEN的表达。结果表明,PTEN可能介导了miR-21在TNBC中的致癌特性。总之,miR-21在TNBC组织和细胞中上调,促进了MDA-MB-468细胞的增殖和侵袭,但对PTEN蛋白的表达起负调控作用。抑制miR-21或过表达PTEN蛋白可能是治疗TNBC患者的有前景的策略。

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