Author:
Li Ke-Xin,Li Jia-Ru,Zuo Sheng-Jia,Li Xudong,Chen Xian-Tong,Xiao Pei-Yi,Li Hui-Tao,Sun Ling,Qian Tao,Zhang Hao-Min,Zhu Dongxing,Yu Xi-Yong,Chen Guojun,Jiang Xue-Yan
Abstract
Abstract
Background
Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further elucidated. This study aimed to explore the function of microRNA-20b-5p (miR-20b-5p) in cardiac development and CHD pathogenesis.
Methods and results
miRNA expression profiling identified that miR-20b-5p was significantly downregulated during a 12-day cardiac differentiation of human embryonic stem cells (hESCs), whereas it was markedly upregulated in plasma samples of atrial septal defect (ASD) patients. Our results further revealed that miR-20b-5p suppressed hESCs-derived cardiac differentiation by targeting tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine, leading to a reduction in key cardiac transcription factors including GATA4, NKX2.5, TBX5, MYH6 and cTnT. Additionally, knockdown of TET2 significantly inhibited cardiac differentiation, which could be partially restored by miR-20b-5p inhibition.
Conclusions
Collectively, this study provides compelling evidence that miR-20b-5p functions as an inhibitory regulator in hESCs-derived cardiac differentiation by targeting TET2, highlighting its potential as a biomarker for ASD.
Funder
National Key Research and Development Program
Guangdong Basic and Applied Basic Research Foundation
National Natural Science Foundation of China
Natural Science Foundation of Guangdong Province
Science and Technology Program of Guangzhou
Open research fund from Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan People’s Hospital
Publisher
Springer Science and Business Media LLC