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引用本文格式: Zhao Xin-Jun,Li Xun,Wang Shu-Heng,Li Jiu-Zhi. GYS2 and p53 restricts tumor growth in HBV-related hepatocellular carcinoma [J]. J. At. Mol. Phys., 2021, 38(3): 031001 (in Chinese) [赵新军,李循,王书恒,李九智. GYS2 与 p53 抑制 HBV 相关的肝癌进展 [J]. 原子与分子物理学报, 2021, 38(3): 031001]
 
GYS2 与 p53 抑制 HBV 相关的肝癌进展
GYS2 and p53 restricts tumor growth in HBV-related hepatocellular carcinoma
摘要点击 207  全文点击 29  投稿时间:2020-09-07  修订日期:2020-10-10
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DOI编号   
中文关键词   糖原合酶2 (GYS2) 与 p53 蛋白  乙肝病毒(HBV)  肝癌(HCC)
英文关键词   Glycogen synthase 2 (GYS2) and p53  Hepatitis B virus x protein (HBx)  Hepatocellular carcinoma(HCC)
基金项目   国家自然科学基金
作者单位E-mail
赵新军 伊犁师范大学 zhaoxinjunzxj@163.com 
李循 新疆维吾尔自治区人民医院  
王书恒 新疆维吾尔自治区人民医院  
李九智 新疆维吾尔自治区人民医院 lijiuzhi2017@163.com 
中文摘要
    本文基于 Hill 动力学与 Michaelis-Menten 方程,建立理论模型研究糖原合酶2 (GYS2) 与 p53 蛋白抑制乙肝病毒(HBV)相关的肝癌进展。理论模型考虑乙肝病毒x蛋白 (HBx)、组蛋白脱乙酰基酶1 (HDAC1)与乙酰化的p53(p53AC) 结合形成复合体,抑制GYS2 表达,以及GYS2通过调控增强稳态 p53(Sp53) 表达,进而抑制肝癌(HCC)的发生发展。研究发现,GYS2 灵敏地调控 Sp53 表达上调,从而使得未乙酰化的Sp53(FSp53) 表达提升,抑制 HCC 的发生发展。部分 Sp53 经过 p300 蛋白乙酰化后与 HBx、 HDAC1 结合形成复合体,通过负反馈抑制 GYS2表达。通过考察不同浓度 HBx 条件下 GYS2 与 FSp53 的动力学特性,我们发现,较高浓度的 HBx 减弱了 GYS2 表达,进而弱化了下游 FSp53 的表达水平。另外,p300 与部分 Sp53 结合,也在一程度上调低了 FSp53 的表达水平,减弱了 FSp53 对 HCC 的抑制程度,从而促进了HCC 发生发展。理论结果符合实验,并进一步揭示 GYS2 与 p53调控的 HCC 的抑癌机理,可为设计阻断乙型肝炎向 HCC 转变通路的治疗方案提供理论依据。
英文摘要
    In this paper, based on Hill kinetics and Michaelis-Menten equation, we built a theoretical model to study the inhibition of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) by glycogen synthase 2(GYS2) and p53. The theoretical model considers the combination of hepatitis B virus x protein (HBx), histone deacetylase 1 (HDAC1) and acetylated p53(p53AC) to form a complex, which suppresses the expression of GYS2. The GYS2 regulates and enhances steady-state p53(Sp53) expression, thereby inhibiting the progression of HCC. We found that GYS2 sensitively regulates the upregulation of Sp53 expression, thereby increasing the expression of unacetylated Sp53 (FSp53) and inhibiting the HCC. A part of Sp53 is acetylated with p300 protein to form a complex with HBx and HDAC1. Thus, it suppresses the expression of GYS2 through negative feedback. By examining the kinetics of GYS2 and FSp53 at different concentrations of HBx, we found that higher HBx concentrations attenuated GYS2 expression, which in turn weakened FSp53 expression. In addition, the combination of p300 and a part of Sp53 also reduced the expression level of FSp53 to a certain extent. Therefore, the inhibition of FSp53 on HCC is weakened, thus promoting the development of HCC. The theoretical results are consistent with the experiment, and further reveal the mechanism of HCC suppression regulated by GYS2 and p53, which can provide a theoretical basis for the design of a treatment plan that blocks the transformation of hepatitis B to HCC.

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