Wu Fang, Yang Qian, Mi Yaping, Wang Feng, Cai Ke, Zhang Yawen, Wang Youhua, Wang Xu, Gui Yonghao, Li Qiang
Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, NHC Key Laboratory of Neonatal Diseases, Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Cardiovascular Center, NHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Front Cell Dev Biol. 2022 Apr 11;10:788799. doi: 10.3389/fcell.2022.788799. eCollection 2022.
As a member of the miR-29 family, miR-29b regulates global DNA methylation through target DNA methyltransferases (DNMTs) and acts as both a target and a key effector in DNA methylation. In this study, we found that miR-29b-3p expression was inversely correlated with DNMT expression in the heart tissues of patients with congenital heart disease (CHD), but whether it interacts with DNMTs in cardiomyocytes remains unknown. Further results revealed a feedback loop between miR-29b-3p and DNMTs in cardiomyocytes. Moreover, miR-29b-3p inhibitor relieved the deformity of hypomethylated zebrafish and restored the DNA methylation patterns in cardiomyocytes, resulting in increased proliferation and renormalization of gene expression. These results suggest mutual regulation between miR-29b-3p and DNMTs in cardiomyocytes and support the epigenetic normalization of miRNA-based therapy in cardiomyocytes.
作为miR-29家族的一员，miR-29b通过靶向DNA甲基转移酶（DNMTs）来调节整体DNA甲基化，并在DNA甲基化过程中既是靶点又是关键效应因子。在本研究中，我们发现先天性心脏病（CHD）患者心脏组织中miR-29b-3p的表达与DNMT的表达呈负相关，但它是否在心肌细胞中与DNMTs相互作用仍不清楚。进一步的结果揭示了心肌细胞中miR-29b-3p与DNMTs之间的反馈回路。此外，miR-29b-3p抑制剂减轻了低甲基化斑马鱼的畸形，并恢复了心肌细胞中的DNA甲基化模式，从而导致细胞增殖增加和基因表达正常化。这些结果表明心肌细胞中miR-29b-3p与DNMTs之间存在相互调节，并支持基于miRNA的心肌细胞治疗的表观遗传正常化。
