AUTHOR=Yang Yiru , Yang Hainan , Lian Xihua , Yang Shuping , Shen Haolin , Wu Shufen , Wang Xiali , Lyu Guorong 

TITLE=Circulating microRNA: Myocardium-derived prenatal biomarker of ventricular septal defects

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.899034

DOI=10.3389/fgene.2022.899034

ISSN=1664-8021

ABSTRACT=Background
Recently, circulating microRNAs (miRNAs) from maternal blood and amniotic fluid have been used as biomarkers for ventricular septal defect (VSD) diagnosis. However, whether circulating miRNAs are associated with foetal myocardium remains unknown.
Methods
Dimethadione (DMO) induced a VSD rat model. The miRNA expression profiles of the myocardium, amniotic fluid and maternal serum were analysed. Differentially expressed microRNAs (DE-microRNAs) were verified by qRT–PCR. The target gene of miR-1-3p was confirmed by dual luciferase reporter assays. Expression of amniotic fluid-derived DE-microRNAs was verified in clinical samples.
Results
MiRNAs were differentially expressed in VSD foetal rats and might be involved in cardiomyocyte differentiation and apoptosis. MiR-1-3p, miR-1b and miR-293-5p were downregulated in the myocardium and upregulated in amniotic fluid/maternal serum. The expression of amniotic fluid-derived DE-microRNAs (miR-1-3p and miR-206) was confirmed in clinical samples. Dual luciferase reporter assays confirmed that miR-1-3p directly targeted SLC8A1/NCX1.
Conclusions 
MiR-1-3p, miR-1b and miR-293-5p are downregulated in VSD myocardium and upregulated in circulation and may be released into circulation by cardiomyocytes. MiR-1-3p targets SLC8A1/NCX1 and participates in myocardial apoptosis. MiR-1-3p upregulation in circulation is a direct and powerful indicator of foetal VSD and is expected to serve as a prenatal VSD diagnostic marker.