MiR-200 suppresses metastases of colorectal cancer through ZEB1.

Abstract

Poor prognosis of some colorectal cancer (CRC) cases largely results from early metastases of CRC to the distal organs. Thus, suppression of the invasion of CRC appears to be crucial therapy. Since microRNAs (miRNAs) play critical roles in the regulation of cancer metastases, identification of the involved miRNAs may provide novel therapeutic targets for CRC treatment. Here, we showed that the levels of miR-200 were significantly decreased and the levels of ZEB1 were significantly increased in the CRC specimens from patients, compared to the paired non-tumor tissue. Moreover, the levels of miR-200 and ZEB1 are inversely correlated. Bioinformatics analyses showed that miR-200 targeted the 3'-UTR of ZEB1 mRNA to inhibit its translation, which was confirmed by luciferase reporter assay. Moreover, miR-200 overexpression inhibited ZEB1-mediated cell invasiveness, while miR-200 depletion increased ZEB1-mediated cell invasiveness in CRC cells. Together, our data suggest that miR-200 suppression in CRC cells may promote ZEB1-mediated cancer metastasis. Our work thus highlights a novel molecular regulatory machinery that regulates metastases of CRC.