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MiR-27a-3p Targeting GSK3β Promotes Triple-Negative Breast Cancer Proliferation and Migration Through Wnt/β-Catenin Pathway

Authors Wu R, Zhao B, Ren X, Wu S, Liu M, Wang Z, Liu W

Received 25 March 2020

Accepted for publication 30 June 2020

Published 24 July 2020 Volume 2020:12 Pages 6241—6249

DOI https://doi.org/10.2147/CMAR.S255419

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Beicheng Sun


Ruizhen Wu, Bingqing Zhao, Xunxin Ren, Shiheng Wu, Mingzao Liu, Zipeng Wang, Wei Liu

The First Affiliated Hospital, School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China

Correspondence: Wei Liu
The First Affiliated Hospital, School of Clinical Medicine, Guangdong Pharmaceutical University, No. 520 Waihuandong Road, University Town, Guangzhou 510006, People’s Republic of China
Tel/ Fax +86-20-39943021
Email liuwei@gdpu.edu.cn

Background: Dysregulation of microRNAs (miRNAs) was found to play crucial roles in varieties of cancers, which affect tumor proliferation and migration. MiR-27a-3p has been identified as a tumor-related miRNA in liver cancer, lung cancer, and colorectal cancer. However, the function of miR-27a-3p in triple-negative breast cancer (TNBC) and its possible molecular mechanisms have still not been elucidated.
Methods: QRT-PCR technique was used to detect the expression of miR-27a-3p in TNBC and normal breast cell lines or the effects of miR-27a-3p knockdown and overexpression in TNBC cell lines. Proliferation and migration were measured by CCK-8 method, colony formation, wound healing, and Transwell assays, respectively. Furthermore, we used a dual-luciferase reporter gene assay and Western blot analysis to identify GSK3β as a target of miR-27a-3p.
Results: In this study, we found that miR-27a-3p expression was significantly elevated in TNBC cell lines. Database analysis suggested that TNBC patients with a high expression of miR-27a-3p have poorer overall survival possibilities. Overexpression of miR-27a-3p promotes TNBC cells proliferation, colony formation, and cell migration in vitro. Nevertheless, dual-luciferase reporter result showed that miR-27a-3p directly targeted the 3ʹ-UTR regions of GSK3β mRNA and negatively regulated its expression. Lastly, we demonstrated that miR-27a-3p inactivates Wnt/β-catenin signaling pathway via targeting GSK3β.
Conclusion: These results indicate that expression of miR-27a-3p was highly expressed in TNBC and promoted tumor progression through attenuating GSK3β and may have a potential molecular-targeted strategy for TNBC therapy.

Keywords: triple-negative breast cancer, miR-27a-3p, GSK3β, Wnt/β-catenin pathway

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