MiR-204/COX5A axis contributes to invasion and chemotherapy resistance in estrogen receptor-positive breast cancers.

Abstract

Breast cancer is the most common cancer among women worldwide, with 70% being estrogen receptor-positive (ER+). Although ER-targeted treatment is effective in treating ER+breast cancer, chemoresistance and metastasis still prevail. Outcome-predictable biomarkers can help improve patient prognosis. Through the analysis of the Array Express database, The Cancer Genome Atlas-Breast Cancer datasets, and breast tumor tissue array results, we found that cytochrome c oxidase subunit 5a (COX5A) was related to poor prognosis of ER+breast cancer. Further studies revealed that COX5A was positively associated with metastasis and chemoresistance in ER+breast cancer. In vitro experiments showed that knockdown of COX5A was accompanied by a decrease in ERα expression, cell cycle arrest, and epithelial-mesenchymal transition blockade, resulting in an inhibition of proliferation and invasion. Knockdown of COX5A enhanced the chemosensitivity of breast cancer cells by decreasing adenosine triphosphate and increasing reactive oxygen species levels. We report that miR-204 can target and inhibit the expression of COX5A, thus, reversing the functions of COX5A in ER+breast cancer cells. We found that COX5A may serve as a prognostic biomarker in ER+breast cancer.