Nogo-B诱导oxLDL降解与肝癌基因激活

Nogo-B induce oxLDL degradation and activation of liver cancer gene

本文基于Hill动力学与Michaelis-Menten方程,建立理论模型研究内质网定位的蛋白Nogo-B诱导调节氧化修饰低密度脂蛋白(oxidized low density lipoprotein(oxLDL))降解与肝癌基因激活.理论模型考虑oxLDL*(降解的oxLDL)-Nogo-B-Yes-associated protein (YAP)通路,研究发现,oxLDL的降解,促进了大量的Lysopho-sphatidic acid (LPA)产生,之后便会提高Hippo信号通路YAP活性,激活了癌基因的表达;经过约5小时Nogo-B表达上调,Nogo-B决定着Nogo-B与Autophagy-related 5 gene(ATG5)的复合体NA,NA调控oxLDL的降解,未降解的oxLDL会诱导Nogo-B表达上调,激活了oxLDL*-Nogo-B-YAP通路,理论结果符合实验结果,并揭示非酒精性脂肪肝病诱发的肝癌的致病机理,可以为设计阻断肝炎向肝癌转变的通路治疗方案提供理论依据.

Based on Hill kinetics and Michaelis-Menten function,we investigate Nogo-B induce oxidized low density lipoprotein(oxLDL) degradation and activation of liver cancer gene. Our model takes oxLDL*(degradating oxLDL)-Nogo-B-Yes-associated protein(YAP) path. We found that the degradation of oxLDL promotes lysopho-sphatidic acid(LPA) largely,and then promotes the activation of YAP in Hippo signaling pathway,which activate expression of liver cancer gene. We also found,after about 5 hours,Nogo-B expression is up-regulated. Nogo-B determined the NA compounded by Nogo-B and autophagy-related 5 gene(ATG5).NA can regulate the degradation of oxLDL. oxLDL also can induce upregulation of Nogo-B expression,which activates oxLDL*-Nogo-B-YAP path. Our theoretical results are consistent with the experimental observations,and provide a fundamental understanding of the nonalcoholic fatty liver disease inducing liver cancer. The results provide a theoretical basis for designing a pathway treatment regimen that blocks the transition of hepatitis to liver cancer.