| Hepatocellular carcinoma(HCC)is a common cause of cancer-related death worldwide,and its incidence continues to rise.However,the mechanism underlying the development and progression of HCC remains unknown.The suppressor of cytokine signaling 2(SOCS2)is a member of the SOCS family and influences the carcinogenesis of multiple types of tumors,but the biological roles of SOCS2 in HCC remain unclear.In this study,we evaluated SOCS2 protein expression in 236 pairs of human HCC and matched non-cancerous liver tissues using immunohistochemistry and found that SOCS2 expression was reduced in HCC tissues compared with matched non-cancerous liver tissues.Moreover,SOCS2 expression levels in HCC tissues were inversely correlated with histological grade and intrahepatic metastasis in HCC patients.To explore the function of SOCS2 in HCC,we stably overexpressed SOCS2 in Li-7,MHCC-97 L and Huh7 cells and knocked down the endogenous expression of SOCS2 in SK-Hep1 and HCC-LY5 cells.The study demonstrated that SOCS2 did not significantly affect cell proliferation and tumorigenicity in HCC cells in vitro and in vivo.However,SOCS2 overexpression significantly inhibited the migration and invasion of HCC cells in vitro and inhibited HCC metastasis in vivo.Consistent with these findings,the knock-down of endogenous SOCS2 enhanced migration and invasion in HCC cells in vitro.Hypoxia can affect the development and metastasis of multiple of tumor.In the present study we found that the expression of SOCS2 in HCC cell lines was significantly downregulated under hypoxia conditions.Overexpression of SOCS2 in HCC cell lines could inhibit the enhanced ability of migration and invasion of HCC cell lines in hypoxia conditions.Taken together,our study demonstrated that SOCS2 inhibited human HCC metastasis and that SOCS2 might contribute to a novel therapeutic strategy for HCC. |