KSHV通过FAM50A重新编程宿主RNA分割,以激活STAT3并驱动瘤细胞转化
Shenyu Sun1,2,3, Karla Paniagua4, Ling Ding1,2
1Cancer Virology Program, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.
bioRxiv : the preprint server for biology
|April 1, 2025
概括
卡波西的肉瘤相关性疹病毒 (KSHV) 劫持宿主RNA拼接机器,特别是FAM50A,以改变SHP2拼接和激活STAT3信号,推动癌症的发展. 这项研究揭示了KSHV瘤发生的一个新机制.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 病毒学 病毒学
背景情况:
- RNA替代拼接在癌症发育中至关重要.
- 卡波西的肉瘤相关性疹病毒 (KSHV) 导致人类恶性瘤,特别是在艾滋病患者中.
- 了解KSHV在细胞转化中的作用至关重要.
研究的目的:
- 为了确定参与KSHV诱导的细胞转换的拼接因素.
- 阐明KSHV驱动的接重编程在瘤发生的机制.
- 研究FAM50A在KSHV介导的转化中的作用.
主要方法:
- 在大鼠介质干细胞 (MM) 和KSHV转化MM细胞 (KMM) 中进行CRISPR-Cas9查.
- 转录组测序以识别差异性的替代拼接事件.
- 对KSHV突变体和FAM50A淘汰细胞的分析.
主要成果:
- 确定了131个不同的替代拼接转录,主要是突变突变跳转.
- 发现FAM50A对KSHV介导的转化,增殖和瘤发生至关重要.
- FAM50A淘汰改变了SHP2剪接,影响了STAT3酸化.
结论:
- KSHV重新编程了涉及FAM50A的宿主拼接机器,以促进瘤发生.
- 在KSHV驱动的转换中,FAM50A介导的SHP2拼接是关键机制.
- 针对FAM50A-SHP2-STAT3轴为KSHV相关癌症提供了潜在的治疗策略.
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