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Aim Type Ⅲ transforming growth factor-beta receptor (TβRⅢ) is a ubiquitously expressed transforming growth factor-beta (TGF-β) superfamily coreceptor with essential roles in embryonic development.Recent studies have defined a role for TβRⅢ in the pathogenesis of human cancers.The present study was designed to explore the role of TβRⅢ in hepatocellular carcinoma (HCC).Methods The expression of TβRⅢ in normal liver tissue and in tumors from HCC patients who underwent surgery resection were detected by real-time PCR and Western blot.The diethylnitrosamine (DEN) -induced liver tumor model in mice was established to detect the expression of TβRⅢ in the progression of HCC by immunohistochemistry (IHC) and Western blot.In vito, the expression of TβRⅢ in stepwise metastatic human HCC cell lines (HepG2, SMMC-7721, MHCC97H, HCCLM3) and normal liver cell line L-02 were measured by Western blot analysis.Wound healing assay was applied to measure the migration of HCC cells after transfection the TβRⅢ siRNA.Results The real-time PCR and Western blot results showed that the expression of TβRⅢ in tumor tissues was lower than that in the non-tumor tissues.The TβRⅢ expression in mice model livers was gradually decreased along with the time passing.Moreover, the expression of TβRⅢ gradually decreased with increasing metastatic potential of HCC cell lines.After transfecting TβRⅢ siRNA in SMMC-7721 cells, the migration ability of SMMC-7721 cells was significantly increased in the presence or absence of TGF-β1 stimulation.Conclusion TβRⅢ may play a essential role in the progression of HCC, and might be a novel suppressor of HCC progression.