Focus: MiR-124 Targets Slug to Regulate Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer.

Abstract

MicroRNAs have been integrated into tumorigenic programs as either oncogenes or tumor suppressor genes. The miR-124 was reported to be attenuated in several tumors, such as glioma, medulloblastoma and hepatocellular carcinoma. However, its roles on cancer remain greatly elusive. Here, we show that the miR-124 expression is significantly suppressed in human breast cancer specimens, which is reversely correlated to histological grade of the cancer. More intriguingly, ectopic expression of miR-124 in aggressive breast cancer cell lines MDA-MB-231 and BT549 strongly inhibits cell motility and invasive capacity, as well as the epithelial-to-mesenchymal transition (EMT) process. Also, lentivirus delivered miR-124 endows MDA-MB-231 cells with the ability to suppress cell colony formation in vitro and pulmonary metastasis in vivo. Further studies has identified the E-cadherin transcription repressor Slug as a direct target gene of miR-124, its downregulation by miR-124 increases the expression of E-cadherin, a hallmark of epithelial cells and a repressor of cell invasion and metastasis. Moreover, knockdown of Slug notably impairs the motility of MDA-MB-231 cells while re-expression of Slug abrogates the reduction of motility and invasion ability induced by miR-124 in MDA-MB-231 cells. These findings highlight an important role for miR-124 in the regulation of invasive and metastatic potential of breast cancer, and suggest a potential application of miR-124 in cancer treatment.

Source: MiR-124 Targets Slug to Regulate Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer. Liang YJ, Wang QY, Zhou CX, Yin QQ, He M, Yu XT, Cao DX, Chen GQ, He JR, Zhao Q. Carcinogenesis. 2012 Dec 17.

Free paper available at:

http://carcin.oxfordjournals.org/content/early/2012/12/16/carcin.bgs383.long