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Background: Recently,it has been confirmed that lncRNA ( long non-coding RNA) CASC2 (Cancer susceptibility candidate 2) could participate in regulating the carcinogenesis and tumor progression to exert its anti-tumor effects.However,the expression and function of CASC2 in hepatocellular carcinoma (HCC) remain unclear.Methods and results: Here,CASC2 was found to be significantly downregulated in HCC tissues and cell lines.And experiments in vitro and in vivo revealed that CASC2 could inhibit cells migration and invasion.Additionally,CASC2 could repress epithelial-mesenchymal transition (EMT) of HCC cells.Further analysis demonstrated that miR-367 was a downstream target of CASC2 in HCC cells.Functionally,miR-367 could promote HCC cells migration,invasion and EMT.Moreover,further investigations showed that FBXW7 (F-box and WD repeat domain containing 7) was a downstream target of miR-367 and CASC2 could exert its suppressive effects on HCC cells via CASC2/miR-367/FBXW7 axis.Clinically,CASC2 and miR-367 were closely correlated with the metastasis-associated clinicopathologic features.Besides,patients both with downregulated CASC2 and with highly expressed miR-367 had the worst survival rate.Conclusions: Overall,we concluded that the CASC2/miR-367/FBXW7 axis may be a ponderable and promising therapeutic target for HCC.