Decreased Expression of hsa-miR-142-3p and hsa-miR-155-5p in Patients with Common Variable Immunodeficiency and Involvement of Their Target Genes and Biological Pathways

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Abstract

Background Common variable immunodeficiency (CVID) is a heterogeneous disorder, and its pathogenesis is often unknown. Monogenic mutations have not been identified in the majority of CVID patients and the pathogenesis process is often unknown. Epigenetic modifications may be involved in unresolved patients. MiR-142 and miR-155 were identified as immune system modulators and are dysregulated in autoimmune and inflammatory diseases. Methods We assessed hsa-miR-142-3p and hsa-miR-155-5p expression in CVID patients 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 expression of the hub genes was investigated in the GEO datasets. Gene Ontology (GO) and pathway enrichment analysis were performed for the target genes. Results hsa-miR-142-3p and hsa-miR-155-5p expression was significantly reduced in CVID patients. Evaluation of the PPI network revealed several hub genes in which pathogenic mutations have been reported in PIDs/CVID, and other hub genes directly contribute to immune responses and the pathophysiology of PIDs. Expression analysis of the hub genes revealed that some of them were significantly dysregulated in CVID patients. Pathway enrichment analysis indicated the involvement of the FoxO-mediated signaling pathway, TGF-β receptor complex, and VEGFR2-mediated vascular permeability. Conclusion 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.

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