MicroRNA-138 suppresses cell proliferation, migration and invasion by targeting smoothened (SMO) in hepatocellular carcinoma

Hedgehog (Hh) signaling pathway is a crucial signal transduction pathway that associated with tumorigenesis in multiple human tissues. Recently, microRNA-138 (miR-138) has been reported to be frequently involved in different tumorigenesis, including hepatocellular carcinoma (HCC). However, whether miR-138 was correlated with Hedgehog (Hh) signaling pathway implicated in the progression of HCC remains unclear. Here, we demonstrated that the expression of miR-138 was downregulated in HCC tissues compared with their matched adjacent nontumor tissues (p < 0.001). Overexpression of miR-138 leaded to impaired cell viability, colony formation, cell migration and invasion of HepG2 cells. Furthermore, smoothened (SMO) was identified as a novel target of miR-138, and the expression of SMO was inhibited by miR-138 overexpression in HepG2 cells. Besides, SMO was upregulated in HCC tissues compared to the matched adjacent normal tissues and its downregulation photocopied the effects of miR-138 overexpression in HepG2 cells. These findings indicate that miR-138 functioned as a tumor suppressor partially via repressing SMO expression in HCC.