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Updated: Jul 23, 2025

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由YTHDF2识别的N⁶-甲基氨酸修饰的circirIRF2通过促进FOXO3核转位来抑制肝纤维化

Xin Chen¹, Sai Zhu², Hai-Di Li¹

¹Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; The Key Laboratory of Anti-inflammatory and Immune Medicines, Anhui Medical University, Ministry of Education, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University, ILD-AMU, Anhui Medical University, Hefei 230032, China.

International journal of biological macromolecules

|July 19, 2023

概括

循环RNA IRF2 (circIRF2) 在肝纤维化中减少. 恢复circIRF2通过调节miR-29b-1-5p和FOXO3来缓解纤维化,这表明circIRF2是治疗点.

科学领域:

分子生物学分子生物学
肝病学肝病学是一种肝病学.
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:

循环RNAs (circRNAs) 通过未知的机制在肝纤维化中发挥作用.
N6-甲基氨酸 (m6A) 修饰影响基因表达,但其在纤维化中circRNA调节中的作用尚不清楚.

研究的目的:

为了研究circIRF2在肝纤维化中的作用.
阐明肝纤维化中 circIRF2 调节和功能背后的分子机制.
评估circIRF2作为肝纤维化的潜在生物标志物或治疗标.

主要方法:

循环RNA测序以识别循环IRF2.2.
在小鼠体内功能增益/丧失研究,以评估circIRF2在纤维生成和分辨率中的作用.
涉及m6A阅读器YTHDF2,miRNA-mRNA相互作用 (miR-29b-1-5p,FOXO3) 和蛋白质定位的机制研究.
微阵列分析以确定circirIRF2-调节的miRNAs.
临床样本分析以比较肝纤维化患者和健康个体的circIRF2水平.

主要成果:

在肝纤维化过程中,circIRF2水平下降,并在解脱过程中恢复.
宫外circIRF2表达减弱肝纤维化和肝星细胞 (HSC) 激活.
circIRF2降低调节导致肝损伤修复和炎症分辨率受损.
YTHDF2识别了m6A修饰的circIRF2,降低了它的稳定性.
circIRF2 泡化miR-29b-1-5p,减轻其对FOXO3的抑制,并促进FOXO3的核转移.
在肝纤维化患者中观察到circIRF2的下调.

结论:

circIRF2是肝纤维化进展和解决的关键调节剂.
m6A修饰和YTHDF2有助于降低肝纤维化中的circIRF2稳定性.
环IRF2/miR-29b-1-5p/FOXO3轴是肝纤维化的一个关键途径.
circIRF2 是肝纤维化的潜在预后标志物和治疗标.

关键词:

在FOXO3中使用FOXO3.肝脏纤维化肝脏纤维化这就是YTHDF2的原因.圆圈IRF2F2F2F2F2 环绕RNAss 的时间.m(6) A6) 一个

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