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微小RNA-22通过靶向沉默调节蛋白1抑制乳腺癌细胞的生长和转移。

MicroRNA-22 inhibits cell growth and metastasis in breast cancer via targeting of SIRT1.

作者信息

Zou Quanqing, Tang Qianli, Pan Yinhua, Wang Xuedi, Dong Xiaofeng, Liang Zhongxiao, Huang Dong

机构信息

Department of Breast Surgery, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China.

Department of Hepatobiliary and Endocrine Surgery, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China.

出版信息

Exp Ther Med. 2017 Aug;14(2):1009-1016. doi: 10.3892/etm.2017.4590. Epub 2017 Jun 13.

Abstract

MicroRNAs (miRs), which are a class of small non-coding RNAs, are key regulators of gene expression via induction of translational repression or mRNA degradation. However, the molecular mechanism of miR-22 underlying the malignant progression of breast cancer, remains to be elucidated. The present study aimed to explore the regulatory mechanism of miR-22 in breast cancer cell growth and metastasis. Reverse transcription-quantitative polymerase chain reaction data revealed that miR-22 was significantly downregulated in breast cancer tissues, compared with adjacent non-tumor tissues. Furthermore, the miR-22 levels were further decreased in stage III-IV, compared with stage I-II breast cancer. In addition, low miR-22 levels were significantly associated with the poor differentiation, metastasis and advanced clinical stages of breast cancer. Sirtuin1 (SIRT1) was demonstrated to act as a direct target gene of miR-22 and its protein expression negatively regulated by miR-22 in the MCF-7 breast cancer cell line. Furthermore, SIRT1 expression levels were significantly upregulated in breast cancer tissues, compared with adjacent non-tumor tissues. SIRT1 levels were observed to be increased in stage III-IV when compared with stage I-II breast cancer. miR-22 overexpression decreased the proliferation, migration and invasion of MCF-7 cells, whereas overexpression of SIRT1 eliminated the suppressive effects of the miR-22 overexpression on the malignant phenotype of MCF-7 cells. The results of the present study therefore suggested that miR-22 demonstrated suppressive effects on breast cancer growth and metastasis via targeting SIRT1, and thus the miR-22/SIRT1 axis may be used as a novel and potential therapeutic target for breast cancer in the future.

摘要

微小RNA(miR)是一类小的非编码RNA,通过诱导翻译抑制或mRNA降解来调控基因表达。然而,miR-22在乳腺癌恶性进展中的分子机制仍有待阐明。本研究旨在探讨miR-22在乳腺癌细胞生长和转移中的调控机制。逆转录定量聚合酶链反应数据显示,与相邻的非肿瘤组织相比,miR-22在乳腺癌组织中显著下调。此外,与I-II期乳腺癌相比,III-IV期乳腺癌中miR-22水平进一步降低。此外,低水平的miR-22与乳腺癌的低分化、转移及临床晚期显著相关。沉默调节蛋白1(SIRT1)被证明是miR-22的直接靶基因,在MCF-7乳腺癌细胞系中,其蛋白表达受到miR-22的负调控。此外,与相邻的非肿瘤组织相比,SIRT1在乳腺癌组织中的表达水平显著上调。与I-II期乳腺癌相比,III-IV期乳腺癌中SIRT1水平升高。miR-22过表达降低了MCF-7细胞的增殖、迁移和侵袭能力,而SIRT1过表达则消除了miR-22过表达对MCF-7细胞恶性表型的抑制作用。因此,本研究结果表明,miR-22通过靶向SIRT1对乳腺癌的生长和转移具有抑制作用,因此miR-2/SIRT1轴未来可能成为乳腺癌新的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d34c/5526179/f9e8aa039e21/etm-14-02-1009-g00.jpg

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