CXCR4 3'UTR functions as a ceRNA in promoting metastasis, proliferation and survival of MCF-7 cells by regulating miR-146a activity

Abstract

CXCR4 is the most common chemokine receptor expressed on tumor cells, and it is closely correlated with cancer cell stemness. This study was carried out to explore whether CXCR4 could function as a competitive endogenous RNA to promote metastasis, proliferation and survival in MCF-7 breast cancer cells. We validated that CXCR4, together with TRAF6 and EGFR, was directly targeted by miR-146a in MCF-7 cells. Overexpression of CXCR4 3'UTR inhibited the activity of miR-146a, thus elevating the expression of CXCR4, TRAF6 and EGFR. These oncoproteins further activated NF-κB pathway and promoted the proliferation, migration, invasion and anti-apoptotic activity of MCF-7 cells. Collectively, our study provided new insights into the function of CXCR4 in breast cancer: it promotes tumor progression as both a protein-coding gene and a non-coding RNA, complicating the mechanism by which oncogenes promote tumor progression.

Keywords: Breast cancer; CXCR4 3′UTR; Competitive endogenous RNA; EGFR; TRAF6; miR-146a.