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MiR-491-5p, as a Tumor Suppressor, Prevents Migration and Invasion of Breast Cancer by Targeting ZNF-703 to Regulate AKT/mTOR Pathway

Authors Guo J, Luo C, Yang Y, Dong J, Guo Z, Yang J, Lian H, Ye C, Liu M

Received 31 August 2020

Accepted for publication 2 December 2020

Published 15 January 2021 Volume 2021:13 Pages 403—413

DOI https://doi.org/10.2147/CMAR.S279747

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Ahmet Emre Eşkazan


Jingyun Guo,* Can Luo,* Yuqin Yang,* Jianyu Dong, Zhaoze Guo, Jinlamao Yang, Huining Lian, Changsheng Ye, Minfeng Liu

Breast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Changsheng Ye; Minfeng Liu
Breast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, People’s Republic of China
Email yechsh2006@126.com; 125556557@qq.com

Background: Large amounts of microRNAs (miRNAs) have been reported to be aberrantly expressed in malignant cancers. MiR-491-5p makes a significant contribution to the inhibition of multiple cancer processes. However, the specific mechanism and function of miR-491-5p and in breast cancer (BC) is still not fully elucidated.
Methods: MiR-491-5p and ZNF-703 expressions or gene transfection effects were identified by RT-qPCR or Western blot in BC tissues or cells. And ZNF-703 expression was monitored through immunohistochemistry method. Cellular function was also confirmed using Transwell assay. Besides, AKT/mTOR pathway-related proteins were analyzed using Western blotting analysis. Moreover, the interplay between miR-491-5p and ZNF-703 was verified through dual-luciferase reporter assay.
Results: miR-491-5p was lowly expressed, ZNF-703 was highly expressed in BC, and miR-491-5p with low expression and ZNF-703 with high expression were associated with poor prognosis of BC patients. Results of cellular function revealed that overexpression of miR-491-5p markedly suppressed BC cell migration and invasion, and knockdown of miR-491-5p had the opposite effect. Besides, mechanism research disclosed that miR-491-5p directly could bind to ZNF-703 and downregulate ZNF-703. Moreover, we proved that ZNF-703 could prominently reverse the influences of miR-491-5p on the migration and invasion of BC cells. More importantly, the data revealed that miR-491-5p repressed AKT/mTOR pathway by ZNF-703 in BC cells.
Conclusion: MiR-491-5p prominently suppresses the metastasis of BC cells through ZNF-703 to regulate AKT/mTOR pathway, indicating that miR-491-5p and ZNF-703 might be served as the potential therapeutic targets for BC.

Keywords: breast cancer, miR-491-5p, ZNF-703, AKT/mTOR pathway, migration and invasion

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