YAP Regulates The Molecular Mechanism Of NF-?B Pathway Activity Through P65

NF-kappa-B pathway is an important inflammatory pathway which has been found as a link between inflammation and cancer,but there are many areas worthy of study.YAP is one of the important members of Hippo pathway and plays an important role in the occurrence and development of tumor.Objective:The purpose of our study is to examine the interaction between YAP and NF-kappa B pathway,and reveal the molecular mechanism of how YAP affects NF-kappa B pathway in HCC cells.Methods:To study the relationship between YAP and P65,HepG2 cells was transfected with siRNA-YAP and YAP-plasmids to slience YAP or over-expressed YAP.Western Blot was used to detect the expression level of proteins.The expression of P65 mRNA was detected by RT-PCR.Immunofluorescence was used to detect the cellular localization of proteins.Luciferase reporter gene experiments were used to detect transcription levels.Results:Overexpression of YAP could increase the nuclear localization and transcription level of P65 in HepG2 cells.In the absence of YAP,the protein and mRNA level of P65 were both decreased.Treatment with LPS known as a agonist of NF-kappa B could upregulate mRNA level of YAP,thus enhance the mRNA level of P65 and PDTC could reverse the over-expression of YAP leading to the increased mRNA level of P65.Conclusion:All the results showed that the regulation of YAP could infect NF-kappa B through the affect of YAP on transcriptional regulation of P65,and this kind of increase could be partly reversed by the inhibitor of NF-kappa B.