Gene Function Of TNFAIP1 In Human Hepatocellular Carcinoma(HCC)

Hepatocellular carcinoma(HCC),is currently one of the most common malignant tumors which has threaten human life and health seriously in China.It is the third leading cause of cancer death in the world and the second in China.Although many scholars have done a lot of research on human HCC,the long-term prognosis of HCC patients after hepatectomy still remains a challenge,largely due to its high recurrence rate and metastasis.Therefore,we need to seek for the molecular mechanisms of HCC progression and novel discovery about useful biomarker as a promising therapy for HCC.Tumor necrosis factor,alpha-induced protein 1(TNFAIP1),also termed as B12,is the first identified tumor necrosis factor?(TNF?)inducible protein.Previous studies have shown that TNFAIP1 has been identified as a potential tumor suppressor,and it may play a significant role in cell growth,cell apoptosis and human diseases.Until now,however,the action mechanism is not extremely clear.In this paper,we mainly focus on the gene function of TNFAIP1 in human HCC.Through Immunohistochemistry assay(IHC),we found that the expression level of TNFAIP1 was significantly lower in HCC tissues compared with normal liver tissues,moreover,its expression levels were correlated with the degrees of tumor differentiation.It revealed that TNFAIP1 was associated with tumor growth and progression of HCC.MTT assay showed that overexpression of TNFAIP1 can inhibit cell growth in Hep G2 cell lines and induce cell growth in reverse.It implies that TNFAIP1 can inhibit cell proliferation ability in HCC.We found that the expression levels of TNFAIP1 in Hep G2 cells were positively associated with concentrations of Hydroxyurea.Moreover,the expression level of TNFAIP1 after serum readdition was increased as the time went by.Further more,it revealed that different expression levels of TNFAIP1 in different stages of cell cycle.These results showed that TNFAIP1 may participate in cell cycle in HCC.In addition,FACS assay demonstrated that TNFAIP1 can inhibit cell cycle in Hep G2 cell lines.Fluorescence Microscope demonstrated that the expression of TNFAIP1 in apoptotic cell nucleus was increased.It indicates that TNFAIP1 may be associated with cell apoptosis in HCC.In addition,FACS assay also showed that TNFAIP1 can induce cell apoptosis in Hep G2 cell lines.Luciferase assay illustrated that TNFAIP1 could upregulate the activity of P53 and P21 transcription while downregulate the activity of Erb B2 trascription,which indicated that TNFAIP1 could inhibit proliferation and induce apoptosis in HCC through activating P53-dependent pathway.In conclusion,our studies found that the expression level of tumor suppressor gene TNFAIP1 in cancer tissues was significantly lower than that of adjacent tissues,and there was a big difference between different degrees of tumor differentiation.It revealed that TNFAIP1 was associated with tumor growth and progression of HCC.TNFAIP1 has an inhibitory effect on cell proliferation and cell cycle of HCC,while TNFAIP1 can significantly induce cell apoptosis.In addition,our study suggested that TNFAIP1 inhibits cell proliferation and induces cell apoptosis in HCC through activating P53-dependent pathway.These studies implied that TNFAIP1 may become a novel molecular target for HCC therapy.