Decreased expression of hsa-miR-142-3p and hsa-miR-155-5p in common variable immunodeficiency and involvement of...

Common variable immunodeficiency (CVID) is the most common symptomatic and heterogeneous type of inborn errors of immunity (IEI). However, the pathogenesis process of this disease is often unknown. Epigenetic modifications may be involved in unresolved patients. MiR-142 and miR-155 were identified as immune system modulators and dysregulated in autoimmune and inflammatory diseases. We assessed hsa-miR-142-3p and hsa-miR-155-5p expression in a selected cohort of unresolved CVID cases and identified experimentally validated targets of these miRNAs. We constructed a protein-protein interaction (PPI) network from the common targets of two miRNAs and determined the hub genes. The hub genes' expression was investigated in GEO datasets. Gene ontology (GO) and pathway enrichment analysis were done for target genes. Hsa-miR-142-3p and hsa-miR-155-5p expression were significantly reduced in CVID patients. Evaluation of the PPI network demonstrated some hub genes in which pathogenic mutations have been reported in IEI, and other hub genes directly contribute to immune responses and the pathophysiology of IEI. Expression analysis of hub genes showed that they were significantly dysregulated in validating the CVID cohort. The pathway enrichment analysis indicated the involvement of the FOXO-mediated signaling pathway, TGFβ receptor complex, and VEGFR2-mediated vascular permeability. Considering the dysregulation of hsa-miR-142-3p and hsa-miR-155-5p in CVID and the known role of their target genes in the immune system, their involvement in the pathogenesis of CVID can be suggested.