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PID1,a new tumor-promoting gene in insulin resistance mediated acceleration of hepatocellular carcinoma development and progression

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中国药理学与毒理学杂志 2017年第10期31卷 977-978页

作者： Ming XIANG Qian-qian XU Na XU Zhong-shi ZHOU Ya-li TUO Cheng TIAN Department of Pharmacology School of PharmacyTongji Medical CollegeHuazhong University of Science and Technology

OBJECTIVE To investigate the effect of phosphotyrosine interaction domain containing 1(PID1,NYGGF4)on promotion of IR and HCC,and explore its underlying *** Lentivirus were used to mediate the knockdown of PID1 in HFD induced IR mouse model as well as ob/ob *** glucose and insulin tolerance were performed 4 weeks after lentivirus ***-based transfection was applied to inducethe liver specific overexpression of *** cytometry was exerted to detect the proportion and function of immune *** T-PCR and Western blot were used to detect the expression of downstream pathways of *** was used to determine the receptor of *** immunoprecipitation(ChI P)was operated to measure the modification of H3K4me3 of PID1 *** PID1 restriction improved insulin resistance,hyperglycemia and fatty ***,hepatic knockdown of PID1 attenuated liver xenografted tumor ***,PID1 liver-specific protooncogenes via hydrodynamics-based transfection established a primary hepatocellular carcinoma mouse model,induced an immunosuppressive environment,with the reduction of CD3^+,CD4^+,CD8^+T cel s,retarded maturation of dendritic cel s(DCs),pronounced differentiation of regulatory T cells(Tregs),and recruitment of *** addition,PID1 overexpression activated proliferation related genes,promoted anti-inflammatory genes,suppressed pro-inflammatory genes,induced glycolysis and lipid metabolism genes to facilitate tumorigenesis in ***,PID1 exerted its tumor-promoting function through binding to epidermal growth factor receptor(EGFR)and activation of downstream MAPK *** such,PID1 exist trimethylation of histone H3 at lysine 4(H3K4me3)modification and IR up-regulated the expression of PID1 by activation the H3K4me3 *** PID1 is a new gene that exerts both liver cancer-promoting and insulin resistance inducing *** accelerates liver cancer

关键词： PID1 insulin resistance hepatocellular carcinoma cancer promoting immunosuppression

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