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MicroRNA-490 inhibits tumorigenesis and progression in breast cancer

Authors Zhao L, Zheng X

Received 7 November 2015

Accepted for publication 20 April 2016

Published 22 July 2016 Volume 2016:9 Pages 4505—4516

DOI https://doi.org/10.2147/OTT.S100037

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Narasimha Reddy Parine

Peer reviewer comments 5

Editor who approved publication: Dr Faris Farassati


Lin Zhao,1 Xin-Yu Zheng1,2

1
Department of Breast Surgery, the First Hospital of China Medical University, 2The First Laboratory, Cancer Institute of China Medical University, Shenyang, People’s Republic of China

Abstract: MicroRNAs are consistently reported to regulate gene expression in all cancer cell types by modulating a wide range of biological processes, including cell proliferation, differentiation, and apoptosis, which are associated with tumor development and progression. Previous studies have revealed that miR-490-3p regulates cell proliferation and apoptosis in cancers, such as hepatocellular carcinoma, lung cancer, bladder cancer, and ovarian carcinoma. In this study, we explored the hitherto unrevealed role of miR-490-3p in breast cancer. We tested miR-490-3p expression in breast cancer tissue and paracarcinoma tissue using reverse transcription–polymerase chain reaction. We also transfected the human breast cancer cell lines MCF-7 and T47D with miR-490-3p; subsequently, we determined the cell phenotype and the expression of Ras homolog gene family member A (RhoA), Bcl-xL, matrix metalloproteinase-9, and P70S6K (P70S6 kinase). Dual-luciferase reporter assay and a xenograft mouse model were used to reveal the roles of miR-490-3p and its target gene RHOA. We found that the levels of miR-490-3p were lower in the breast cancer tissue than in the paracarcinoma tissues. The overexpression of miR-490-3p suppressed breast cancer cell proliferation and promoted early stage apoptosis. Western blotting results revealed that the miR-490-3p overexpression reduced RhoA, Bcl-XL, matrix metalloproteinase-9, and P70S6K protein expression. The dual-luciferase reporter assay confirmed that RhoA is a target of miR-490-3p. The xenograft mouse model confirmed that miR-490-3p overexpression suppressed tumor growth and reduced RhoA expression. Our results indicate that miR-490-3p acts as oncosuppressive microRNA to inhibit breast cancer tumorigenesis and progression by targeting RhoA directly. It may contribute to breast cancer diagnosis and treatment.

Keywords: breast cancer, miR-490-3p, RhoA, tumorigenesis and progression
 

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