Long noncoding RNA uc.4 inhibits cell differentiation in heart development by altering DNA methylation

Abstract

In previous studies, we have demonstrated that long noncoding RNA uc.4 may influence the cell differentiation through the TGF‐β signaling pathway, suppressed the heart development of zebrafish and resulting cardiac malformation. DNA methylation plays a significant role in the heart development and disordered of DNA methylation may cause disruption of control of gene promoter. In this study, methylated DNA immunoprecipitation was performed to identify the different expression levels of methylation regions. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were also performed to identify the possible biological process and pathway that uc.4 may join, associated with Rap1 signaling pathway, gonadotropin‐releasing hormone signaling pathway, and Calcium signaling pathway. We found that the distribution of differentially methylated regions peaks was mainly located in intergenic and intron regions. Altogether, our result showed that differentially methylated genes are significantly expressed in uc.4‐overexpression cells, providing valuable data for further exploration of the role of uc.4 in heart development.

CHDGKB: a knowledgebase for systematic understanding of genetic variations associated with non-syndromic congenital heart disease

“…The top eight significant enriched terms of KEGG pathways along with number of genes for isolated and non-isolated CHD can be seen in Figure 8 . Series of MAPK signaling pathways ( 23 ), signaling pathways regulating pluripotency of stem cells ( 24 ) and Rap1 signaling pathway ( 25 ) are essential for occurrence of both isolated and non-isolated CHD.…”

Differential lncRNA/mRNA expression profiling and ceRNA network analyses in amniotic fluid from foetuses with ventricular septal defects

“…LncRNAs can activate or repress gene expression in several ways to affect foetal heart development. For example, lncRNA uc.4 inhibits cell differentiation in heart development by altering DNA methylation ( Zhang et al, 2018 ). Enhancer lncRNAs are involved in the maintenance of cardiac stem cell pluripotency and cardiomyocyte differentiation ( Devaux et al, 2015 ).…”

Maternal body fluid lncRNAs serve as biomarkers to diagnose ventricular septal defect: from amniotic fluid to plasma

“…For instance, lncRNA SAP30-2:1 is downregulated in CHDs and regulates cell proliferation by targeting HAND2 (Ma et al, 2021); lncRNA-HA117 is upregulated in the myocardial tissue of Tetralogy of Fallot (ToF) children and negatively correlated with the prognosis (Wang et al, 2018). At the pre-transcriptional level, lncRNA can act as an enhancer or alter DNA methylation to inhibit cardiomyocyte differentiation and maintain cardiac stem cell pluripotency (Devaux et al, 2015;Zhang et al, 2019). At the post-transcriptional level, lncRNA-associated competitive endogenous RNA (ceRNA) is an essential epigenetic patterning of the genome.…”