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自噬介导肝细胞癌耐药的相关机制

张润兵 史婷婷 伍杨 张久聪 郑晓凤

引用本文:
Citation:

自噬介导肝细胞癌耐药的相关机制

DOI: 10.12449/JCH241128
基金项目: 

中央高校优秀青年团队培育项目 (1001451201);

甘肃省自然科学基金青年项目 (22JR5RA1012)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:张润兵负责课题设计,资料分析,撰写论文;史婷婷、伍杨参与收集数据,修改论文;张久聪、郑晓凤负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    张久聪, zhangjiucong@163.com (ORCID: 0000-0003-4006-3033)

    郑晓凤, zhengxf19892013@126.com (ORCID: 0009-0002-9660-1224)

The mechanism of autophagy inducing drug resistance of hepatocellular carcinoma

Research funding: 

The Central University Outstanding Youth Team training Project (1001451201);

Youth Project of Gansu Provincial Natural Science Foundation (22JR5RA1012)

More Information
  • 摘要: 肝细胞癌(HCC)治疗抵抗是制约其疗效的重要因素。自噬是一种多步骤、多靶点的过程,与肿瘤细胞的增殖和凋亡密切相关。同时,自噬与肿瘤治疗抗性之间也存在显著串扰。因此,自噬可能是肿瘤细胞在临床干预后阻碍细胞死亡的关键因素之一。转化生长因子-β、上皮间充质转化、长链非编码RNA是导致HCC耐药的重要因素。本文从转化生长因子-β、上皮间充质转化及长链非编码RNA这三个角度,探讨其介导复杂的分子网络诱导自噬的发生而影响HCC耐药性的可能机制,为提高HCC治疗敏感性探索新的思路。

     

  • 图  1  自噬机制示意图

    Figure  1.  Schematic diagram of the mechanism of autophagy

    表  1  自噬和 HCC 耐药中的lncRNA

    Table  1.   lncRNA in autophagy and HCC resistance

    lncRNA 自噬蛋白 细胞 药物 表达状态 主要观点 参考文献
    KCNQ1OT1 BECN1

    SK-HEP-1

    SK-HEP-1/DDP(耐药细胞)

    顺铂 在HCC细胞中表达上调 KCNQ1OT1靶向miR-338-3p,抑制SK-HEP-1/DDP细胞的自噬,提高SK-HEP-1/DDP细胞对顺铂的敏感性 35
    NEAT1

    LC3

    ATG3

    Huh7

    HepG2

    索拉非尼 在HCC细胞中表达上调 NEAT1通过调节miR-204/ATG3通路促进HCC细胞的自噬,增强HCC对索拉非尼的耐药性 36
    SNGH16 LC3

    Hep3B

    Hep3B/So(耐药细胞)

    索拉非尼 在HCC细胞中表达上调 SNGH16通过下调miR-23b-3p的表达,促进HCC细胞自噬,增加其对索拉非尼的耐药性 37
    CRNDE ATG4B

    SMMC-7721

    HepG2

    Hep3B

    Huh7

    索拉非尼 在HCC组织及细胞中表达上调 lncRNA CRNDE通过促进ATG4B的表达介导自噬,增加HCC细胞对索拉非尼的耐药性 38
    SNHG1

    LC3

    BECN1

    SR-HCC 索拉非尼 在HCC细胞中表达上调 SNHG1通过上调SLC3A2激活Akt通路,诱导自噬发生,使 HCC对索拉非尼耐药 39
    HULC

    LC3

    P62

    Hep3B

    Huh7

    奥沙利铂 在HCC组织及细胞中表达上调 HULC通过调节miR-383-5p/VAMP2轴促进HCC发自噬并减弱HCC对奥沙利铂的化疗敏感性 40
    BBOX1-AS1 LC3

    Hep3B

    Huh7

    索拉非尼 在HCC组织及细胞中表达上调 BBOX1-AS1通过调节miR-361-3p/PHF8轴促进细胞自噬,降低索拉非尼在HCC细胞中的细胞毒性 41
    HOTAIRM1 BECN1

    Huh7

    HepG2

    仑伐替尼 在HCC组织及细胞中表达上调 HOTAIRM1下调miR-34a激活细胞自噬,诱导HCC对仑伐替尼产生耐药性 42

    注:KCNQ1OT1,KCNQ1重叠转录物1;NEAT1,核富集丰富的转录本1;SNGH16,小核仁RNA宿主基因16;CRNDE,结直肠肿瘤差异表达;SNHG1,小核仁RNA宿主基因1;HULC,肝细胞癌上调长链非编码RNA;BBOX1-AS1,γ-丁酰甜菜碱羟化酶1反义RNA 1;HOTAIRM1,HOXA转录本反义RNA1。

    下载: 导出CSV
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  • 收稿日期:  2024-02-04
  • 录用日期:  2024-03-29
  • 出版日期:  2024-11-25
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