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

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.

Role of miRNA in Cardiovascular Diseases in Children—Systematic Review

“…Expressions of two miRNAs (miR-454, miR-518f) were found to be higher in children with DCM when compared to the control group [59]. The level of miR-454 was also significantly higher in Egyptian children with DCM and in patients with familial DCM caused by Lamin A/C (LMNA) gene mutations [60,61]. It is suggested that this miRNA targets insertion/deletion gene polymorphisms of angiotensin-converting enzyme (ACE), which consequently links it to the pathogenesis of DCM [62].…”

“…Unlike Coşkun et al, Fayez et al (2022) reported that the miR-194 level was significantly higher in the child population [60]. miR-194 targets heparin-binding EGF-like growth factor (HBEGF) gene which impairs the phosphorylation of ERBB2/B4 tyrosine kinase receptors and in turn leads to severe DCM [67].…”

“…Furthermore, Coşkun et al showed that expression levels of miR-618, miR-875-3p, miR-205, miR-194, miR-302a, miR-147, miR-544, miR-99b, miR-155, miR-218 were significantly lower in the DCM group [59]. miR-875-3p was also significantly lower in Egyptian children with DCM [60]. miR-875-3p targets the myopalladin gene (MYPN) and miR-618 targets mutations on tropomyosin alpha (TPM1).…”

Genome-wide characterization of SOS1 gene family in potato (Solanum tuberosum) and expression analyses under salt and hormone stress

“…PlantRegMap 14 was used to functionally re-annotate the proteome of up or down-regulated genes and to plot gene ontology (GO) annotations. Protein-protein interaction (PPI) enrichment was computed by STRING 15 (Fayez et al, 2022) tool, in which Cytoscape software was used for reconstructing the PPI network, modules and to detect the relationship between overall targeted genes.…”