Elevated expression of circulating CDR1as in childhood dilated cardiomyopathy patients; Expanding MAPK signaling pathway role in dilated cardiomyopathies pathogenesis.

Abstract

Background Circular RNAs (circRNAs) are non-coding RNAs resulting from back splicing of pre-mRNA. circRNAs exhibit higher stability with multiple functional modes. Thus, this circRNAs characteristic make it a promising entity for the development of diagnostic tools and therapies for human disease. In the present study, we mainly aimed to evaluate two circRNAs CDR1as and has-circRNA_105039 as noninvasive biomarkers for childhood dilated cardiomyopathy and ventricular septal defects patients. Methods Fold change of CDR1as and has-circRNA_105039 was detected by qRT-PCR in 101 participants. The diagnostic accuracy of CDR1as was determined by receiver operating characteristic (ROC) analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEEG) pathway analyses were performed to predict CDR1as/miRNAs and CDR1as/proteins interaction networks related to congenital ventricular septal defects (VSD) and childhood dilated cardiomyopathy (DCM). Results CDR1as showed significant higher fold change (FC = 2.8) in DCM group than controls and VSD groups. Experimental evidence-based GO and KEGG pathways analysis showed that has-miR-7-5p and hsa-miR-619 targeted 3'UTR of three mRNAs involved in MAPK signaling pathway. Conclusion Upregulated CDR1as may influence the level of has-miR-7-5p and hsa-miR-619 in childhood DCM patients, and further relieve the inhibitory effect of these miRNAs on kinases of the MAPK signaling pathway.