NEW INSIGHTS OF MIR-145 FUNCTION AND REGULATION IN HUMAN BREAST CANCER.

Abstract

miR-145 is down-regulated in the majority of human cancers, including breast cancer (BC). However, its role remains largely unknown. Here, I provide evidence for miR-145 induced anti-proliferative and pro-apoptotic effect in several BC cell lines, which was not detected in BC cells lacking a functional TP53 gene and exhibiting an estrogen receptor alfa (ESR1) negative status. I found that miR-145 anti-proliferative effects were dependent upon TP53 activation and that activation of TP53 could in turn stimulates miR-145 expression. I also found that miR-145 could repress the expression of ESR1 protein by direct interaction with two sites within its gene coding sequence. My findings support the existence of a positive regulatory loop where miR-145 directly targets ESR1 and indirectly activates TP53, which in turn sustains miR-145 expression and reinforces miR-145 overall effects on proliferation and apoptosis