miR-199a-5p regulates beta 1 integrin through Ets-1 to suppress invasion in breast cancer

• Published in: Cancer science Vol. 107; no. 7; pp. 916 - 923
• Main Authors: Li, Wentong, Wang, Hui, Zhang, Jinbao, Zhai, Limin, Chen, Weijuan, Zhao, Chunling
• Format: Journal Article
• Language: English
• Published: 01.07.2016
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12952

Increasing evidence has revealed that miR-199a-5p is actively involved in tumor invasion and metastasis as well as in the decline of breast cancer tissues. In this research, overexpression of miR-199a-5p weakened motility and invasion of breast cancer cells MCF-7 and MDA-MB-231. Upregulation of Ets-1 increased breast cancer cell invasion, but the mechanism by which miR-199a-5p modulates activation of Ets-1 in breast cancer was not clarified. We investigated the relationship between miR-199a-5p and Ets-1 on the basis of 158 primary breast cancer case specimens, and the results showed that Ets-1 expression was inversely correlated with endogenous miR-199a-5p. Overexpression of miR-199a-5p reduced the mRNA and protein levels of Ets-1 in MCF-7 and MDA-MB-231 cells, whereas anti-miR-199a-5p elevated Ets-1. siRNA-mediated Ets-1 knockdown phenocopied the inhibition invasion of miR-199a-5p in vitro. Moreover, luciferase reporter assay revealed that miR-199a-5p directly targeted 3'-UTR of Ets-1 mRNA. This research revealed that miR-199a-5p could descend the levels of beta 1 integrin by targeting 3'-UTR of Ets-1 to alleviate the invasion of breast cancer via FAK/Src/Akt/mTOR signaling pathway. Our results provide insight into the regulation of beta 1 integrin through miR-199a-5p-mediated Ets-1 silence and will help in designing new therapeutic strategies to inhibit signal pathways induced by miR-199a-5p in breast cancer invasion. Our results provide insight into the regulation of beta 1 integrin through miR-199a-5p-mediated Ets-1 silence and help in designing new therapeutic strategies to inhibit signal pathways induced by miR-199a-5p in breast cancer invasion.