基础医学与临床 ›› 2023, Vol. 43 ›› Issue (5): 762-770.doi: 10.16352/j.issn.1001-6325.2023.05.0762

• 研究论文 • 上一篇    下一篇

载脂蛋白E通过降低高尔基体膜蛋白73表达抑制小鼠肝癌细胞系增殖

侯孟杰1, 赵娜1,2, 黄富强1, 王亚南1, 刘芳铭1*   

  1. 1.中国医学科学院基础医学研究所 北京协和医学院基础学院 生理学系,北京 100005;
    2.山东第一医科大学附属省立医院 输血科,山东 济南 250000
  • 收稿日期:2023-01-10 修回日期:2023-02-23 出版日期:2023-05-05 发布日期:2023-04-26
  • 通讯作者: *lfmpumc@163.com
  • 基金资助:
    中国医学科学院医学与健康科技创新工程(2021-1-I2M-018)

Apolipoprotein E negatively regulates Golgi membrane protein 73 to inhibit the proliferation of mouse liver cancer cell lines

HOU Mengjie1, ZHAO Na1,2, HUANG Fuqiang1, WANG Yanan1, LIU Fangming1*   

  1. 1. Department of Physiology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005;
    2. Department of Blood Transfusion, Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250000, China
  • Received:2023-01-10 Revised:2023-02-23 Online:2023-05-05 Published:2023-04-26
  • Contact: *lfmpumc@163.com

摘要: 目的 探究载脂蛋白E(APOE)与高尔基体膜蛋白73(GP73)之间的调控关系,并明确其对肝癌细胞增殖的影响。方法 分析在线网站肝癌数据库中APOE与GP73的相关性;小鼠分为对照及Apoe缺失组、对照及Gp73缺失组;细胞分为Gp73敲低组、Apoe敲低组(转染小干扰RNA或感染慢病毒)及相应对照;GP73过表达组、APOE过表达组(转染过表达质粒)及相应对照;GP73低表达组(转染小干扰RNA或雷帕霉素处理)及对照组。Western blot检测APOE和GP73的蛋白表达;CCK8法检测细胞增殖。结果 在肝癌中GP73与APOE的表达负相关(P<0.001);在小鼠肝脏、肾脏组织中,Gp73缺失不影响APOE表达,而Apoe缺失导致GP73表达上调(P<0.001);在肝癌细胞系中,GP73改变不影响APOE表达,而APOE过表达或敲低引起GP73相应下调或上升(P<0.01);降低APOE促进肝癌细胞系增殖(P<0.01);下调GP73抑制Apoe敲低促进的小鼠肝癌细胞系增殖(P<0.001)。结论 APOE负调控GP73。而通过降低GP73表达,从而抑制APOE下调介导的小鼠肝癌细胞系增殖。这种调控关系可能是肝癌的一个病理机制和潜在治疗靶点。

关键词: 载脂蛋白E, 高尔基体膜蛋白73, 负调控, 细胞增殖

Abstract: Objective To explore the potential regulatory relationship between apolipoprotein E (APOE) and Golgi membrane protein 73 (GP73) for elucidating its significance in the proliferation of liver cancer cells. Methods Online databases were checked for correlation between APOE and GP73 expression in liver cancer. Mice were divided into control and Apoe knockout groups, control and Gp73 knockout groups. Cell lines were divided into Gp73 knockdown group, Apoe knockdown group (transfected with small interference RNA or infected with lentivirus) and corresponding control, GP73 over-expression group, APOE over-expression group (transfected with over-expression plasmids) and corresponding control, GP73 low expression group (transfected with small interference RNA or treated with rapamycin) and control group. Western blot was used to detect APOE and GP73 protein expression, and CCK8 assay was used to detect cell proliferation. Results GP73 was negatively correlated with APOE in liver cancer (P<0.001).GP73 deficiency did not alter APOE expression, while APOE deficiency enhanced GP73 expression in mice(P<0.001). Consistently, GP73 did not affect APOE expression but APOE negatively regulated GP73 expression in liver cancer cells (P<0.01). Besides, Apoe knockdown promoted mouse liver cancer cell proliferation(P<0.01), which was reversed by GP73 inhibition (P<0.001). Conclusions APOE suppresses GP73 expression. Inhibition of GP73 may reverse APOE knockdown-accelerated cell proliferation. Therefore, APOE inhibits cell proliferation through suppression of GP73 which may contribute to liver cancer progression and be targeted for the treatment of hepatic cancer.

Key words: apolipoprotein E, Golgi membrane protein 73, negative regulation, cell proliferation

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