Research Paper|Volume 12, Issue 11|pp 10246—10258

miR-623 suppresses cell proliferation, migration and invasion through direct inhibition of XRCC5 in breast cancer

Qing Li¹, Jiangtao Liu², Yanli Jia², Tingting Li³, Mei Zhang¹

¹Department of General Surgery, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan 250000, Shandong, P.R.China
²Department of Internal Medical Oncology, Binzhou Central Hospital, Binzhou 251700, Shandong, China
³Anesthesia Department, Binzhou Central Hospital, Binzhou 251700, Shandong, China

Received: October 24, 2019Accepted: February 25, 2020Published: June 5, 2020

Copyright © 2020 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background/Aims: MicroRNAs (miRNAs) are short, non-coding RNA molecules that control gene expression trough negative translational regulation. MiR-623 is a tumor suppressor, and it’s function and mechanism in breast cancer has not been reported.

Results: Exogenous overexpression of miR-623 suppressed cell proliferation, migration and invasion, meanwhile, but promoted cell apoptosis. MiR-623 knockdown displayed opposite results. Overexpression of miR-623 resulted in the downregulation of CDK4/6 as well as the inhibition of the phosphatidylinositol-3-kinase (PI3K)/Akt and Wnt/β-Catenin signaling pathways. MiR-623 knockdown displayed opposite results. Results of the reporter assay revealed that the luciferase activity was decreased in XRCC5-wt cells, suggesting that miR-623 could directly combine with 3’ UTR of XRCC5. MiR-623 significantly suppressed XRCC5 expression, which is critical for miR-623-induced proliferation and migration block in breast cancer cells.

Conclusion: miR-623 suppressed cell proliferation, migration and invasion through downregulation of cyclin dependent kinases and inhibition of the phosphatidylinositol-3-kinase (PI3K)/Akt and Wnt/β-Catenin pathways by targeting XRCC5.

Methods: miR-623 was either overexpressed in breast cancer cell lines through exogenous transfection or knocked down by specific siRNA. Cell proliferation, migration and invasion were examined using CCK-8, colony formation and transwell assay. The direct target of miR-623 was verified using luciferase reporter gene assay.