m6A修改促进EMT和割抵抗性前列腺癌的转移通过UpregulatingNFIB
Feng Shu1, Hao Liu2, Xiaohui Chen1
1Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China.
Cancer research
|March 27, 2024
概括
核因子I/B (NFIB) 通过促进表皮细胞到介质细胞转变 (EMT) 来驱动雄激素受体阴性化耐性前列腺癌 (CRPC) 的转移. 准N6-甲基氨酸 (m6A) /NFIB通路为CRPC治疗提供了一个新的策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 由于治疗选择有限,受体 (AR) 阴性割耐性前列腺癌 (CRPC) 存在重大临床挑战.
- 了解AR阴性CRPC的分子驱动因素对于开发有效疗法至关重要.
研究的目的:
- 调查核因子I/B (NFIB) 在AR阴性CRPC进展和转移中的作用.
- 阐明调节机制,包括N6-甲基氨酸 (m6A) 修饰,参与AR阴性CRPC中NFIB上调.
主要方法:
- 在患者衍生的AR阴性CRPC瘤和细胞系中分析NFIB表达.
- 评估NFIB对表皮细胞转介质 (EMT) 和细胞迁移的影响.
- 对参与EMT的NFIB直接转录目标的调查.
- 在体内转移模型.
- 在NFIB和TRIM8mRNA上对m6A修饰的分析.
主要成果:
- 在AR阴性CRPC中,NFIB被上调,并与EMT表型相关.
- 失去NFIB抑制了EMT和CRPC细胞迁移,NFIB直接调节了E-cadherin和vimentin.
- 在体内研究证实了NFIB在转移中的作用.
- N6-甲基氨酸 (m6A) 修饰通过通过YTHDF2.2.增加mRNA稳定性来调节AR阴性CRPC中的NFIB.
- ALKBH5下调增加了TRIM8mRNA的m6A修饰,增强了NFIB蛋白的稳定性.
结论:
- 由m6A修饰驱动的NFIB的升级促进了AR阴性CRPC中的EMT和转移.
- m6A/NFIB轴代表了预防和治疗AR阴性CRPC转移的潜在治疗标.
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