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维生素D受体调节14类甲基转移酶,以减轻结肠炎相关的结肠直肠癌
Zheng Wang1, Lingjuan Jiang2, Xiaoyin Bai3
1Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China; Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
维生素D受体 (VDR) 和METTL14通路保护大肠炎相关结直肠癌 (CAC). 维生素D疗法可能为治疗这种疾病提供了一个新的策略.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 结肠炎相关结直肠癌 (CAC) 是性结肠炎 (UC) 的严重并发症,结果不佳.
- 维生素D受体 (VDR) 对于保持肠壁完整性和调节UC和CAC的炎症至关重要.
- 在UC和CAC患者中观察到m6A相关基因,包括METTL14的减少表达.
研究的目的:
- 在UC和CAC的背景下调查METTL14和VDR之间的关联.
- 探索VDR-METTL14轴在预防和治疗CAC中的治疗潜力.
主要方法:
- 使用CAC.的阿佐西米 (AOM) /德克斯硫酸 (DSS) 鼠标模型.
- 给予维生素D和使用Vdr-knockout小鼠.
- 使用NCM460和DLD-1细胞与VDR激动剂和淘汰/过度表达技术进行了体外研究.
- 进行了机制研究,以确定VDR在METTL14表达中的调节作用.
主要成果:
- 在AOM/DSS模型中,维生素D治疗增加了METTL14表达,并减少了瘤负担.
- 在Vdr-Knockout小鼠中,METTL14的降低和瘤发生的增加.
- 在体外,VDR激活可提高METTL14的调节,而VDR阻断可降低METTL14并促进癌细胞的增殖.
- 发现VDR通过促进体结合来调节METTL14表达,影响SOX4,DROSH和PHLPP2.
结论:
- VDR-METTL14轴在结肠炎相关的结肠直肠癌中起着重要的保护作用.
- 准VDR-METTL14通路为预防和治疗CAC提供了一个有前途的治疗策略.
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