JMJD2D稳定并与HBx蛋白合作,促进HBV转录和复制
Xu Kong1,2, Zuofeng Liu1,3, Ruyi Zhang1,2
1Cancer Research Center, School of Medicine, Xiamen University, Xiamen, China.
JHEP reports : innovation in hepatology
|September 13, 2023
概括
针对宿主因子JMJD2D提供了一种针对慢性乙型肝炎 (CHB) 感染的新策略. 抑制JMJD2D通过稳定HBx蛋白和增强HBV转录来减少乙型肝炎病毒 (HBV) 复制.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 乙型肝炎病毒 (HBV) 感染是一个重大的全球健康挑战.
- 协同封闭圆形DNA (cccDNA) 的转录调节是持续性慢性乙型肝炎 (CHB) 感染的关键因素.
- 针对宿主因子进行ccccDNA沉默是一种新的治疗策略.
研究的目的:
- 研究Jumonji C域含有 (JMJD2) 蛋白子家族成员 (JMJD2A-2D) 在HBV复制中的作用.
- 确定JMJD2D影响HBVccDNA转录和复制的机制.
- 评估JMJD2D作为CHB的潜在治疗点.
主要方法:
- 基于lentivirus的RNA干扰用于抑制HBV感染细胞中的JMJD2A-2D表达.
- 产生了JMJD2D淘汰赛小鼠用于体内实验.
- 协同免疫沉,无处不在和染色体免疫沉试验被用于研究JMJD2D-HBx相互作用和ccDNA调节.
主要成果:
- 在HBV感染的小鼠肝脏和人类肝瘤细胞中,JMJD2D的表达显著上调.
- 下调JMJD2D抑制了ccccDNA转录和HBV复制.
- 通过抑制TRIM14介导的降解,JMJD2D稳定HBx,并作为HBx的联合激活剂,增强HBV复制. 一种JMJD2D抑制剂 (5C-8-HQ) 抑制了HBV复制.
结论:
- 通过稳定HBx,JMJD2D在调节HBV转录和复制方面发挥着至关重要的作用.
- 确定JMJD2D是一种潜在的诊断生物标志物,也是CHB和HBV相关肝癌的有前途的药物标.
- 向JMJD2D代表了治疗慢性乙型肝炎感染的新型翻译方法.
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