MicroRNA-664 Targets Insulin Receptor Substrate 1 to Suppress Cell Proliferation and Invasion in Breast Cancer.

Abstract

A large number of microRNAs (miRNAs) have been previously demonstrated to be dysregulated in breast cancer (BC), and alterations in miRNA expression may affect the initiation and progression of BC. This study showed that miR-664 expression was obviously reduced in BC tissues and cell lines. Resumption of the expression of miR-664 attenuated the proliferation and invasion of BC cells. The molecular mechanisms underlying the inhibitory effects of BC cell proliferation and invasion by miR-664 were also studied. Insulin receptor substrate 1 (IRS1) was identified as a novel and direct target of miR-664. In addition, siRNA-mediated silencing of IRS1 expression mimicked the suppressive effects of miR-664 overexpression in BC cells. Rescue experiments demonstrated that recovered IRS1 expression partially antagonized the inhibition of proliferation and invasion of BC cells caused by miR-664 overexpression. Thus, miR-664 may serve as a tumor suppressor in BC by directly targeting IRS1. Moreover, miR-664 downregulation in BC may contribute to the occurrence and development of BC, suggesting that miR-664 may be a novel therapeutic target for patients with BC.