MiR-337-3p suppresses proliferation of epithelial ovarian cancer by targeting PIK3CA and PIK3CB

Abstract

Epithelial ovarian cancer (EOC) is responsible for nearly 140,000 deaths worldwide each year. MicroRNAs play critical roles in cancer development and progression. The function of microRNA miR-337-3p has been described in various cancers. However, the biological role of miR-337-3p and its molecular mechanisms underlying EOC initiation and progression have not been reported. Here, we reported that the expression of miR-337-3p is down-regulated in EOC tissues and low expression of miR-337-3p is correlated with advanced pathological grade for patients. Ectopic expression of miR-337-3p inhibited proliferation and induced apoptosis and cell cycle arrest in G0/G1 phase of EOC cells. PIK3CA and PIK3CB were revealed to be direct targets of miR-337-3p for reducing the activation of PI3K/AKT signaling pathway. PIK3CA and PIK3CB were discovered to affect cell proliferation of EOC cells in combination, and only when overexpressed simultaneously in miR-337-3p-expressing cells, could fully restore cell proliferation. In vivo investigation confirmed that miR-337-3p is a tumor suppressor that control expression of PIK3CA and PIK3CB encoded protein: p110α and p110β. Altogether, our results demonstrate that miR-337-3p is a tumor suppressor in EOC that inhibits the expression of PIK3CA and PIK3CB.

Keywords: AKT; Cell cycle; Cell proliferation; PI3K signaling.