在前列腺癌中通过FOXM1/PCNA轴调节N6-甲基氨酸修饰的cirRPS6KC1调节的细胞衰老
Xuan Shu1, Jiahe Yi1, Jiangfeng Li1
1Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Cancer Center, Zhejiang University, Hangzhou 310058, China.
Cellular signalling
|November 16, 2024
概括
这项研究揭示了N6-甲基氨酸修饰如何稳定前列腺癌 (PCa) 中的circRPS6KC1 . 然后,这种循环RNA通过FOXM1/PCNA途径影响细胞衰老.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 前列腺癌 (PCa) 是全球男性的主要癌症.
- 循环RNAs (circRNAs) 和N6-甲基氨酸 (m6A) 修饰与PCa进展有关.
- 在PCa中m6A修饰的circRNAs的特定作用仍然在很大程度上未知.
研究的目的:
- 研究m6A修饰在前列腺癌中的circRNAs中的作用.
- 确定参与PCa进展的新型circRNA及其调节机制.
- 阐明circRPS6KC1对PCa细胞衰老的功能影响.
主要方法:
- 循环RNA测序以识别PCa中差异表达的循环RNA.
- 西部涂抹和RT-qPCR用于评估蛋白质和RNA水平.
- RNA免疫沉 (RIP) 测试以确认m6A修饰和结合蛋白质.
- 路西法酶记者测定验证miRNA海绵活动.
- 细胞衰老测试和细胞周期分析.
主要成果:
- 确定circRPS6KC1作为PCa.中的新型,上调的circRNA.
- 证实METTL3和YTHDF1能够调解m6A修饰和circRPS6KC1.1的稳定.
- 在PCa细胞中抑制circRPS6KC1诱导的细胞衰老.
- 循环RPS6KC1作为miR-761海绵,调节FOXM1表达的功能.
- FOXM1介导PCNA转录和p21降解,导致p53独立的p21上调.
结论:
- 在前列腺癌中,由METTL3和YTHDF1修改的N6-甲基氨酸稳定了circRPS6KC1.
- 稳定circRPS6KC1通过通过FOXM1/PCNA轴抑制细胞衰老,促进PCa的进展.
- 这项研究揭示了一种新的调节途径,涉及m6A修饰的circRNAs在PCa病变发生过程中.
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