Zhang Lei, Xing Meiling, Wang Xingang, Cao Weihong, Wang Haibo
Department of Breast Surgery, The Affiliated Hospital of Qingdao University Qingdao 266003, Shandong, China.
Department of Blood Transfusion, Yantai Yuhuangding Hospital Yantai 264000, Shandong, China.
Int J Clin Exp Pathol. 2017 Aug 1;10(8):8361-8368. eCollection 2017.
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.
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