MicroRNA-497 downregulation contributes to cell proliferation, migration, and invasion of estrogen receptor alpha negative breast cancer by targeting estrogen-related receptor alpha.

Metastasis has become the main challenge for treatment of estrogen receptor alpha (ERα) negative breast cancer. Here, we found a negative correlation between miR-497 and estrogen-related receptor alpha (ERRα), a nuclear receptor overexpressed in ERα negative breast cancer. Targeted inhibition of ERRα by si-RNA increased miR-497 expression while overexpression of ERRα inhibited miR-497 expression. Further investigation showed that miR-497 targeted ERRα by binding to the 3'UTR region of ERRα. Luciferase assay and ChIP assay confirmed that ERα directly regulated the transcription of miR-497, suggesting that loss of ERα lowered miR-497 level in ERα negative breast cancer. Further, overexpression of miR-497 not only inhibited ERRα expression but also reduced MIF level and MMP9 activity, which led to significant decreases in cell proliferation, migration, and invasion of ERα negative breast cancer. Taken together, our findings suggested that, in ERα negative breast cancer, the low level of ERα reduced miR-497 expression, which promoted ERRα expression that enhanced cell proliferation, migration, and invasion by increasing MIF expression and MMP9 activity.