循环瘤细胞聚类调节RNA剪接和多化以促进转移
Quanyou Wu1, Zhaoru Gu2, Bingqing Shang3
1Division of Abdominal Cancer, Department of Medical Oncology, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, China; State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
循环瘤细胞 (CTC) 集群由于RNA调节的改变,显示出更高的转移潜力. 替代拼接和多化影响CTC集群恶性病变和转移的转录后变化.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 基因组学就是基因组学.
背景情况:
- 循环瘤细胞 (CTC) 集群具有比单个CTC更大的转移潜力.
- 驱动CTC集群转移的机制,特别是转录后RNA调节,尚不清楚.
研究的目的:
- 为了比较单个CTC和CTC集群之间的替代拼接 (AS) 和替代多化 (APA) 配置文件.
- 阐明RNA调节在CTC集群恶性瘤和转移潜力的作用.
主要方法:
- 在单个CTC和CTC集群中对AS和APA配置文件进行比较分析.
- 识别不同规范的AS事件和APA因素.
- 分析3' UTR长度变化及其功能影响.
主要成果:
- 在单个CTC和CTC集群之间观察到AS事件 (∼20%) 和APA配置文件的显著差异.
- 对SRSF6的差异拼接与CTC集群恶性瘤的增加有关.
- CTC集群表现出全球3' UTR延长,受PPP1CA等APA因子的控制,增强细胞周期进展和抗压力.
- 在CTC集群中,H2AFY mRNA的较长3' UTRs通过增强的稳定性和翻译促进了扩散和入侵.
结论:
- 转录后RNA调节,包括AS和APA,在CTC集群的转移潜力中发挥着关键作用.
- 改变的RNA配置文件有助于CTC集群的攻击性表型,促进瘤转移.
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