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自噬介导肝细胞癌耐药的相关机制
DOI: 10.12449/JCH241128
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。
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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。Abstract: Treatment resistance of hepatocellular carcinoma （HCC） is an important factor restricting its treatment outcome. Autophagy is a process involving multiple steps and targets and is closely associated with the proliferation and apoptosis of tumor cells. At the same time， there is significant crosstalk between autophagy and tumor treatment resistance. Therefore， autophagy may be one of the key factors hindering tumor cell death after medical intervention. Transforming growth factor-β （TGF-β）， epithelial-mesenchymal transition （EMT）， and long non-coding RNA （lncRNA） are important factors leading to drug resistance of HCC. This article discusses the possible mechanism of TGF-β， EMT， and lncRNA mediating complex molecular networks and inducing drug resistance of HCC， in order to provide new ideas for improving the sensitivity of HCC treatment.
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Key words:
- Carcinoma， Hepatocellular /
- Autophagy /
- Drug Resistance， Neoplasm
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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。
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