PDE4a predicts poor prognosis and promotes metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma

Abstract

Phosphodiesterases (PDEs) was found to be involved in a variety of cancer pathologies by modulating the degradation of levels of cAMP/cGMP. However, the prognostic significance and biological effect of PDE4a in hepatocellular carcinoma (HCC) have not been understood completely. In the present study, PDE4a expression was detected in a cohort of HCC and matched adjacent liver tissues (n = 210) by immunohistochemistry staining and Western immunoblotting assay, And in vitro experiments were conducted to determine the effect of PDE4a on metastatic capacity of HCC cells. The data here displayed that the majority of HCC patients had higher PDE4a expression in tumor tissues compared to matched adjacent liver tissues and enhanced PDE4a expression in tumor tissues was associated positively with HBV infection, liver cirrhosis, higher serum AFP level, advanced TNM stage, vascular embolus, intrahepatic metastases and portal vein tumor thrombus (PVTT). Survival analyses suggested that higher PDE4a was indicated the poor prognosis of HCCs after liver resection. Ectopic expression of PDE4a in Huh7 cells leaded to significant repression of E-cadherin and up-regulated the expression of N-cadherin and Vimentin, and facilitated migration and invasion abilities. Silencing PDE4a in MHCC97h cells acquired the opposite results. Taken together, PDE4a triggered EMT in HCC cells and acted as a predictive factor candidate and a potential therapeutic target for HCC.