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. 2025 Jun 4;21(2):247-254.
doi: 10.5114/aic.2025.151804. eCollection 2025 Jun.

Role of circulating microRNAs in tetralogy of Fallot

Claudia Huesca-Gomez  1 , Nadia Gonzalez-Moyotl  1 , Silvia Romero-Maldonado  2 , Reyna Samano  3 , Ricardo Gamboa  1
Affiliations

Role of circulating microRNAs in tetralogy of Fallot

Claudia Huesca-Gomez et al. Postepy Kardiol Interwencyjnej. .

Abstract

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.

Keywords: children; microRNAs; pediatric; tetralogy of Fallot.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Levels of miR-221-3p (p = 0.001) (A), miR-26-5p (p = 0.07) (B), miR-21-5p (p = 0.008) (C), miR-155-5p (p = 0.05) (D), and miR-144-3p (p = 0.001) (E), in the serum of patients with TOF compared with the control group
Figure 2
Figure 2
ROC curve analysis. A ROC model was performed to differentiate between the control and congenital heart disease groups. The whole population was analyzed, 23 TOF patients and 45 controls. The optimal cut-off point was defined through Youden’s score index to maximize the sum of sensitivity and specificity of miR-21-5p, miR-26-5p, and miR-144a-3p
Figure 3
Figure 3
The interaction network generated by geneMANIA shows how specific key genes are in the development of cardiac tissues. Each node represents a gene, with lines indicating regulatory interactions
See this image and copyright information in PMC

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