模型化研究HBx与CREB诱发肝癌的一种物理机制  

Modeling study on a physical mechanism of HBx and CREB inducing hepatocellular carcinoma

作　　者：马军仁 赵新军 MA Jun-Ren;ZHAO Xin-Jun(Xinjiang Laboratory of Phase Transitions and Microstructures of Condensed Matter Physics,Yi Li Normal University,Yining 835000,China;Laboratory of Micro-Nano Electro Biosensors and Bionic Devices,Yi Li Normal University,Yining 835000,China)

机构地区：[1]伊犁师范大学物理科学与技术学院新疆凝聚态相变与微结构实验室,伊宁835000 [2]伊犁师范大学微纳电传感器技术与仿生器械实验室,伊宁835000

出　　处：《原子与分子物理学报》2022年第6期28-36,共9页Journal of Atomic and Molecular Physics

基　　金：伊犁师范大学校级一般项目(2021YSYB100);国家自然科学基金(22163011);伊犁师范大学研究生创新项目(2021YSGS2141)。

摘　　要：本文基于Hill动力学与Michaelis-Menten方程,建立理论模型研究乙型肝炎病毒(HBx)通过与环磷腺苷效应元件结合蛋白(CREB)相互作用促进肝癌(HCC)发生发展的一种物理机制.理论模型考虑HBx-CPAP(中心体P4.1相关蛋白)-AKT(蛋白激酶B)-GSK3(糖原合成酶激酶3)-P53通路信号传导特性.研究发现,CREB对HBx有扩增效应,较高浓度的CREB使得P53抑癌功能下降,并促使炎性因子(NF-κB)呈现出二次增长,为HBx诱发HCC提供了炎性微环境.CREB还会调控AKT呈现二次增长,影响细胞糖原代谢,在一定程度上促使了HCC的发生发展.理论结果符合实验,进一步揭示了HBx通过与CREB相互作用促进HCC发生发展的一种物理机制,可为设计阻断肝炎向肝癌转变通路的治疗方案提供理论依据.In this paper,based on Hill dynamics and Michaelis-Menten equation,we built a theoretical model to study the mechanism of Hepatitis B virus(HBx)promoting the development of hepatocellular carcinoma(HCC)through interaction with CREB(cAMP-response element binding protein).The theoretical model takes the HBx-CPAP(centrosome P4.1 associated protein)-AKT(protein kinase B)-GSK3(Glycogen Synthase Kinase3)-P53 pathway into consideration.We found that with the increase of CREB concentration(CREB concentration=0.01-0.05),HBx has amplification effect,which leads to the significant decrease of tumor suppressor function of P53.The overexpression of inflammatory factor(NF-κB)creates an inflammatory microenvironment.CREB also regulates the secondary growth of AKT and affects cell glycogen metabolism.These factors contribute to the occurrence and development of HCC.Our theoretical results are consistent with the experimental observations,and provide a fundamental understanding of the HBx promoting the development of HCC through interaction with CREB.The results provide a theoretical basis for designing treatment plans that blocks the transition of hepatitis to HCC.

关 键 词：HBX CREB 肝癌 

分 类 号：Q492[生物学—生理学]