乙型肝炎病毒DNA整合基因CCDC91具有致癌性,是肝细胞癌的潜在治疗标
Mengge Li1, Shusheng Wu2, Huiqin Luo1
1Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Communications biology
|July 19, 2025
概括
乙型肝炎病毒融入CCDC91基因驱动肝癌 (肝细胞癌) 的进展. 这一发现揭示了涉及CCDC91和LDHA的新机制,影响治疗耐药性.
科学领域:
- 在瘤学瘤学.
- 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) 整合与肝细胞癌 (HCC) 的发展有关.
- 不完全理解HBV驱动的基因变异和癌症发病机制,特别是关于HBV插入的基因.
研究的目的:
- 为了研究HBV DNA的整合到与癌症相关的基因在HCC.
- 阐明CCDC91在HBV相关的HCC病原和索拉芬尼布耐药性中的作用.
主要方法:
- 聚合分析和HBV捕获测序以确定HBV整合部位.
- 基因表达分析,体外和体内功能测定用于CCDC91.1.
- RNA测序和共免疫沉以探索分子相互作用.
主要成果:
- 在HCC组织中发现了重复的HBVDNA整合到CCDC91基因中.
- CCDC91的表达与HBVDNA存在相关,并且在HCC上升调节,促进恶性瘤和更短的存活时间.
- 该Ct-HBx蛋白调节CCDC91,激活LDHA,驱动有氧糖解和HCC进展,并赋予索拉芬尼布耐药性.
结论:
- CCDC91是一种新的,HBV集成的,与HCC相关的基因.
- Ct-HBx/CCDC91/LDHA轴促进HCC的进展和对索拉芬尼布的抵抗.
- 了解这种途径可以了解HCC机制和潜在的治疗策略.
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