Role of miR-138 in the regulation of larynx carcinoma cell metastases.

Abstract

The cases of larynx carcinoma (LC) with poor prognosis largely result from the distal metastases of the primary tumor. Since microRNAs (miRNAs) play critical roles during cancer metastases, determination of the involved miRNAs in the regulation of the LC metastases may provide novel therapeutic targets for LC treatment. Here, we studied the LC specimens from the patients and found that the levels of miR-138 were significantly decreased and the levels of ZEB2, a critical factor that regulates cancer cell invasiveness, were significantly increased in LC, compared to the paired normal larynx tissue. Metastatic LC appeared to contained lower levels of miR-138. Moreover, miR-138 and ZEB2 inversely correlated in LC specimens. Bioinformatics analyses showed that miR-138 targeted the 3'-untranslated region (3'-UTR) of ZEB2 mRNA to inhibit its translation, which was confirmed in a luciferase reporter assay. Further, miR-138 overexpression inhibited ZEB2-mediated cell invasiveness, while miR-138 depletion increased ZEB2-mediated cell invasiveness in LC cells. Together, our data suggest that miR-138 suppression in LC cells may promote ZEB2-mediated cancer metastases. Thus, miR-138 appears to be an intriguing therapeutic target to prevent metastases of LC.