MicroRNA‐26a‐5p inhibits breast cancer cell growth by suppressing RNF6 expression

Abstract MicroRNA‐26a‐5p (miR‐26a‐5p) has been reported to be involved in the tumorigenesis of several tumors, but its function in breast cancer is still unknown. In this study, miR‐26a‐5p was found significantly downregulated in both of the breast cancer tissues and cell lines, and low expression of miR‐26a‐5p predicted a poor prognosis for breast cancer patients. Overexpression of miR‐26a‐5p could significantly inhibit breast cancer cell growth. Further studies revealed that overexpression of miR‐26a‐5p downregulated the protein levels of Cyclin D1, CDK4, and CDK6, but upregulated the expression levels of p21, p27, and p53. In mechanism, miR‐26a‐5p targeted the 3′UTR of ring finger protein 6 (RNF6) mRNA and inhibited RNF6 expression in breast cancer cells. Moreover, overexpression of miR‐26a‐5p inhibited RNF6/ERα/Bcl‐xL axis in breast cancer cells. In contrast, inhibiting miR‐26a‐5p upregulated RNF6/ERα/Bcl‐xL axis. Further studies indicated that miR‐26a‐5p mediated RNF6/ERα/Bcl‐xL axis through regulating the stability of ERα protein. Collectively, downregulation of miR‐26a‐5p plays essential roles in breast cancer by mediating RNF6/ERα/Bcl‐xL axis, which might provide important implications for the therapeutics of breast cancer.