Role of circulating microRNAs in tetralogy of Fallot

Introduction:
Congenital heart disease (CHD) is the most common malformation from birth. The severity of the different forms of CHD varies extensively from superficial mild lesions with follow-up for decades without any treatment to complex cyanotic malformations requiring urgent surgical intervention. One of the most common severe forms of CHD is tetralogy of Fallot (TOF), characterized by a misalignment of the canal septum leading to a deviation of the aorta to the right. microRNAs (miRs) are crucial in cardiac development, giving rise to possible phenotypes in CHD.

Aim:
We aimed to evaluate the expression of miRs in 23 children with TOF and 45 controls and correlate them with the clinical characteristics of both the children and the mothers.

Material and methods:
We analyzed the miRNA expression of miR-21-5p, miR-155-5p, miR-221-3p, miR-26a-5p, and miR-144-3p by RT-qPCR.

Results:
In this study, we found that miR-221-5p, miR-21-5p, and miR-144-3p exhibited a significant difference in expression compared to controls. Through bioinformatics analysis, we found that the target genes of analyzed mIRs are members of the AKT1, SMAD, TNF-α, and FOX families. All have in common that they are associated with different cellular pathways that lead to cell cycle changes, cell growth, and apoptosis, mainly in hypoxic conditions.

Conclusions:
The expression levels of miRs in pediatric patients may contribute to the development of TOF. Additionally, the high expression of miR-221-5p, miR-21-5p, and miR-144-3p in children with TOF is associated with genes associated with many cellular pathways involved in TOF development.