Study On FoxA2Influenced Liver Cancer Cell Proliferation

Primary liver cancer is one of the common malignant tumors. The invasiveness of livercancer cell is strong, and the prognosis of liver cancer cell is poor,so liver cancer’s death rateranked No.2among all the cancer’s death rates. Although the mechanisms for thedevelopment of liver cancer incidence is still exploring, we know that the occurrence anddevelopment of liver cancer is a process of multi-gene participation, and multi-step advance.p53pathways play important roles in the development of HCC. The transcription factorswhich can regulate cell cycle can interact with P53, and they can enhance the activity of p21promoter upstream, stimulate the expression of p21, regulate the p53-p21pathway.FoxA2(Forkhead-box A2) is one of the FOX transcription factor family members, andis an important metabolic liver transcriptional activator of genes. As we all know that p21is acell cycle control protein which can widely inhibits the kinase activity. p21can regulatecyclin-dependent kinases CDK negatively, by inhibiting the formation of cyclin-CDKcomplexesIn this study, we constructed a high expression of lentiviral vector that can expressFoxA2and made a high titer FoxA2lentivirus. By using FoxA2lentivirus and specific FoxA2siRNA in HCC cells respectively, we have found that the over-expression of FoxA2repressthe cell proliferation, while the knock-down of FoxA2accelerates the proliferation of cells.The next analysis of RT-PCR have showed that increased mRNA levels of p53and p21areboth detected after the over expression of FoxA2, indicateing that FoxA2can activate thetranscription of p53and p21.All those resμlts have showed that FoxA2, as a repressor oftumor growth, may inhibit HCC cell’s proliferation by stimulating the expression of p53andp21. Our study may provide a possible direction for the gene therapy of hepatocellularcarcinoma.