miR-454-3p and miR-194-5p targeting cardiac sarcolemma ion exchange transcripts are potential noninvasive diagnostic biomarkers for childhood dilated cardiomyopathy in Egyptian patients

Abstract

Abstract Background Childhood dilated cardiomyopathy (CDCM) is the most common cardiomyopathy in children and it is risk factor to heart failure and sudden death. Most of the different etiologic factors which have been postulated to DCM are idiopathic, and its pathogenesis remains uncertain. So it was worth investigating the potential DCM pathogenicity models to establish early noninvasive diagnosis parameters especially in CDCM patients. Beside that miRNAs in the circulatory blood are genetically considered the best option for noninvasive diagnosis; also, implementation of miRNAs as early diagnostic markers for children with DCM is urgent because those children have high risk to sudden heart death. We aimed to identify discriminator diagnostic circulatory miRNA expression levels in CDCM patients. Results The expression levels of miR-454-3p and miR-194-5p were found significant upregulated (p value = 0.001 and 0.018; CI 95%, respectively), while miR-875-3p was found significant downregulated (p value = 0.040; CI 95%). A receiver operating characteristic (ROC) curve analysis showed significant AUC = 1.000 and 0.798 for miR-454-3p and miR-194-5p, respectively, and the optimal discriminated diagnostic cut-points were computed by index of union (IU) method. Enrichment analysis for the potential targeted mature mRNAs by miR-454-3p and miR-194-5p pointed that Ca, Na and K ions homeostasis in cardiac sarcolemma consider potential CDCM pathogenicity model. Conclusions miR-454-3p and miR-194-5p are highly influencing noninvasive biomarkers for CDCM, and further circulatory miRNAs-implicated studies are highly recommended.

Keywords

• Childhood dilated cardiomyopathy
• Noninvasive diagnostic biomarkers
• miRNAs
• Cardiac sarcolemma
• Gene ontology analysis