MiR-124 Targets Slug to Regulate Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer
Menée in vitro et in vivo, cette étude met en évidence le rôle joué par le micro-ARN 124 dans la régulation des processus invasif et métastatique d'un cancer du sein
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.
http://carcin.oxfordjournals.org/content/early/2012/12/16/carcin.bgs383.abstract