The epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cells (CSCs)-like properties are essential steps in the metastasis and postsurgical recurrence of hepatocellular carcinomas (HCCs). The molecular mechanisms involved, however, remain obscure. As determined by an miRNA microarray analysis, there was lower expression of miR-148a in poorly differentiated HCC tissues relative to well-differentiated HCC tissues. MHCC97H and MHCC97L (HCC cells with migratory capacity) and HCC tissues with various differentiation status were selected for further investigation. The results showed that miR-148a levels inversely correlated with the differentiation status of HCC tissues. In MHCC97H and MHCC97L cells, over-expression of miR-148a blocked the EMT process, attenuated the expression of CD90 and CD44 (biomarkers for liver cancer stem cells), and inhibited their migratory capacity. Via TargetScan and microRNA.org algorithms, miR-148a was predicted to bind to the Wnt1 mRNA 3'-UTR. Wnt1 was confirmed as a target gene of miR-148a in HCC cells, and the Wnt signal pathway was determined to be involved in the miR-148a-mediated inhibition of EMT and CSCs-like properties of MHCC97H cells. Moreover, the expression of miR-148a in nonmetastatic HCC tissues was higher than that in metastatic HCC tissues. The results suggest that miR-148a inhibits the metastasis of HCCs by blocking EMT and CSCs-like properties through effects on the Wnt signaling pathway.
Keywords: Wnt pathway; cancer stem cells-like properties; epithelial to mesenchymal transition; hepatocellular carcinoma; metastasis; microRNA-148a.
© 2013 Wiley Periodicals, Inc.