TRAIP functions as an oncogene in hepatocellular carcinoma via Rb/EZH2/p21 signaling pathway

Abstract Background The TRAF-interacting protein (TRAIP) has been identified as a master regulator of DNA damage and implicated in the progression of human cancers. Yet the underlying mechanism of TRAIP-mediated malignant phenotype remains unclear. Methods The expression of TRAIP in hepatocellular carcinoma (HCC) was examined by qRT-PCR, western blot and immunohistochemistry. The clinical significance of TRAIP was determined by Kaplan-Meier survival analyses. The biological function and the underlying mechanism of TRAIP in HCC progression were investigated, using cellular and molecular biological experiments.Results Here, we show that TRAIP is upregulated in HCC and functions as an oncogene via Rb/EZH2/p21 signaling. Overexpression of TRAIP, at both mRNA and protein levels, is correlated with more aggressive clinicopathological features, and unfavorable overall and disease-free survivals. In vitro experiments demonstrate that ectopic expression of TRAIP enhances, whereas knockdown of TRAIP attenuates HCC cell proliferation. Further data show that TRAIP interacts with SPAG5 in HCC cells, which results in the stabilization of TRAIP protein. TRAIP overexpression suppresses the expression of Rb, subsequently leading to the increase of EZH2 and decrease of p21. Re-expression of Rb and p21 significantly inhibits TRAIP-mediated cell growth. Conclusion Collectively, our findings suggest TRAIP exert oncogenic activity and have prognostic and therapeutic potential in HCC.