MiR-205 suppresses tumor growth, invasion, and epithelial-mesenchymal transition by targeting SEMA4C in hepatocellular carcinoma

Abstract

Growing evidence indicates that microRNAs are involved in tumorigenesis and progression of hepatocellular carcinoma (HCC). However, the functional mechanisms of miR-205 in HCC remain largely unknown. Here,we demonstrate thatmiR-205 expression was significantly down-regulated in HCC tissues and cell lines and was correlatedwithmetastatic pathologic features and shorter disease-free and overall survival. Overexpression of miR-205 dramatically inhibited HCC cell proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT) in vitro, and tumor growth in vivo. We subsequently identified semaphorin 4C (SEMA4C) as a novel target ofmiR-205. Furthermore, high expression levels of SEMA4C were frequently found in HCCtissues and were associated with poor prognosis. Ectopic expression of SEMA4C restored the suppressive effect of overexpressedmiR- 205onmigration, invasion, and EMT. Takentogether, our findings provide new insight into the critical role of miR-205 in regulating tumor growth, invasion, and EMT of HCC, suggestingmiR-205 may serve as a promising therapeutic target and novel prognostic indicator for patients with HCC.