Nogo-B诱导oxLDL降解与肝癌基因激活

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.

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

Based on Hill kinetics and Michaelis-Menten function, we investigate Nogo-B induce oxLDL degradation and activation of liver cancer gene. Our model takes oxLDL* (degradating oxLDL)-Nogo-B-YAP path. We found the degradation of oxLDL promoted LPA largely, and then promoted 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 ATG5. NA can regulate the degradation of oxLDL. oxLDL also can induce upregulation of Nogo-B expression, which activate oxLDL*-Nogo-B-YAP path. Our theoretical results are consistent with the experimental observations, and provide a fundamental understanding of the non- -alcoholic 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.