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通过调节与雄激素功能相关的TRIM68基因,RNA N6-甲基氨酸修饰结合蛋白YTHDF1促进前列腺癌的进展
Qihong Nie1, Xiaoyuan Wu2, Yongming Huang2
1Department of Oncology, Ganzhou People's Hospital, Ganzhou, 341000, Jiangxi, Jiangxi, China.
European journal of medical research
|December 2, 2023
概括
这项研究揭示了YTHDF1介导的m6A修饰调节了前列腺癌 (PC) 的进展. YTHDF1针对TRIM68,影响雄激素受体 (AR) 信号传递和PC细胞行为.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 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:
- 与雄激素受体 (AR) 相关的基因在前列腺癌 (PC) 发病过程中至关重要.
- 在PC中N6-甲基氨酸 (m6A) 修饰的作用,特别是关于AR相关基因,仍然在很大程度上未被探索.
- 了解这些分子机制对于开发向疗法至关重要.
研究的目的:
- 为了研究m6A甲基化调节PC病变的机制.
- 阐明PC中m6A修饰和AR相关基因之间的直接关系.
- 确定YTH域含有蛋白1 (YTHDF1) 在PC进展中的作用.
主要方法:
- 定量逆转录聚合酶连锁反应 (qRT-PCR) 来评估基因表达.
- 细胞测试 (流细胞计,伤口愈合,Transwell) 以评估PC细胞活力,亡,迁移和入侵.
- RNA免疫沉测序 (MeRIP-seq) 用于识别m6A目标.
- 在体内实验中,在裸体小鼠中使用皮下异种移植.
主要成果:
- 在用AR抑制剂治疗的PC细胞中,YTHDF1的表达显著下调.
- YTHDF1敲击降低了AR水平,细胞活力和PC细胞中的m6A甲基化.
- TRIM68被确定为YTHDF1的直接标;YTHDF1和TRIM68都抑制了PC细胞的增殖和转移,而TRIM68的过度表达逆转了这些影响.
结论:
- 通过m6A修饰,YTHDF1在PC进展中发挥着关键作用.
- YTHDF1-TRIM68轴调节AR功能并影响前列腺癌的发展.
- 这一发现突出了YTHDF1作为前列腺癌的潜在治疗点.
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