Study Of Biological Effects And Mechanism Of GATA4 In Hepatocellular Carcinoma

Objective: The high mortality and poor prognosis of hepatocellular carcinoma(HCC)have raised the public attention.Gene therapy is considered as a promising treatment option for cancer;thus,finding a new therapeutic target for hepatocellular carcinoma is urgently needed.GATA4 is a tumor suppressor gene in multiple cancers,but its role in HCC is unclear.In this study,we explored the function and mechanism of GATA4 in the development of HCC.Methods : RT-PCR and qPCR were used to detect the mRNA expression of GATA4 in HCC cells and tissues.Cell viability assay,transwell,colony formation and flow cytometry assays were applied to examine different aspects of biological effects of GATA4 in vitro.Xenografts,immunohistochemistry and TUNEL assays were performed to evaluate the effect of GATA4 on tumorigenicity in vivo.Western blotting,immunofluorescence and ?-galactosidase staining were used to investigate the mechanism underlying the function of GATA4.Results:We found that GATA4 was decreased or silenced in 15/19(79%)HCC tissues.Restoring the expression of GATA4 induced G0/G1 phase arrest,promoted apoptosis,suppressed HCC proliferation in vitro and inhibited HCC tumor growth in vivo.Our data further showed that the ectopic expression of GATA4 induced cellular senescence through regulating nuclear factor-?B(NF-?B)and inducing mesenchymal to epithelial transition(MET).Conclusion: Our data demonstrated that by inducing cellular senescence and MET,GATA4 plays a crucial role as a tumor suppressor in HCC.It may thus be a potential cancer therapeutic target for HCC.