小型HBV表面抗原通过KIAA1429依赖的CCR9m6A修饰驱动HCC中的regorafenib耐药性
Zhao Lv1, Lijuan Liu1,2, Jian You3
1State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Journal of medical virology
|August 29, 2024
概括
乙型肝炎病毒 (HBV) 小表面抗原 (SHBs) 通过m6A修饰通过调高C-C动机化学因子受体9 (CCR9) 来促进肝癌 (HCC) 的进展和对regorafenib的抗性. CCR9是一种潜在的生物标志物,用于HBV相关的HCC中生存率较低的潜在生物标志物.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 乙型肝炎病毒 (HBV) 感染与肝细胞癌 (HCC) 的药物耐药性有关,特别是针对 sorafenib.
- 乙型肝炎病毒对另一种HCC治疗药物regorafenib耐药性的作用不太清楚.
- C-C 基因化学因子受体9 (CCR9) 与癌症进展有关.
研究的目的:
- 调查HBV在HCC中对regorafenib耐药性的作用.
- 确定预测HBV相关HCC生存的生物标志物.
- 阐明 HBV 诱导的 HCC 进展和耐药性背后的分子机制.
主要方法:
- 对GEO数据库 (GSE87630) 和临床HCC样本的分析.
- 单变量和多变量考克斯回归分析.
- 使用HBV结构蛋白和HCC细胞系进行体外功能检测.
- AAV-HBV小鼠模型和m6A水平分析.
- mRNA稳定性测试和m6A修饰部位的识别.
主要成果:
- 在与HBV相关的HCC中,CCR9的表达很高,与HBsAg阳性相关,并预测整体存活率较低.
- HBV 小表面抗原 (SHBs) 调高了CCR9的表达.
- SHBs增强了HCC细胞的增殖,迁移,入侵,并通过CCR9.9促进了对regorafenib的抗性.
- 乙型肝炎病毒感染增加了全球N6-甲基氨酸 (m6A) 水平.
- SHB提高了m6A水平,通过KIAA1429介导的m6A修饰在特定的部位上调节和稳定了CCR9mRNA.
结论:
- 通过KIAA1429介导的m6A修饰,SHBs通过上调和稳定CCR9mRNA来促进HCC进展和对regorafenib的耐药性.
- 在与HBV相关的HCC中,CCR9作为对regorafenib耐药性的潜在预后生物标志物和治疗标.
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