MiR-148a suppresses invasion and induces apoptosis of breast cancer cells by regulating USP4 and BIM expression.

Abstract

MicroRNAs (miRs), acting as tumor suppressor or oncogenes genes, play a critical role in controlling tumor invasion, metastasis and survival via regulating a variety of targets. MiR-148a has been observed low expressed in several types of human cancers, and overexpression of miR-148a inhibits tumorigenesis. However, the molecular mechanisms of miR-148a-mediated these effects are largely elusive. Therefore, the aim of this study was to evaluate the biological function and molecular insight on miR-148a mediated roles in breast cancer cell. In the present study, we demonstrated that low miR-148a expression was observed in breast cancer cells compared to the normal human breast cells. Transfection with miR-148a inhibited growth, migration, invasion, and induced apoptosis in MDA-MB-231 cells. Ubiquitin-specific protease 4 (USP4) and BIM was the potential target of miR-148a. Indeed, miR-148a overexpression decreased expression of USP4 and increased BIM expression. Additionally, we revealed that miR-148a exerts its pro-apoptotic functions through upregulation of BIM, and miR-148a exerts its anti-invasive functions through downregulation of USP4. We therefore suggested that miR-148a is a tumor suppressor, which could be a promising therapeutic target for breast cancer.