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Decreased Expression of Hsa-Mir-142-3P and Hsa-Mir-155-5P in Common Variable Immunodeficiency and Involvement of Their Target Genes and Biological Pathways Publisher Pubmed



Ranjbarnejad T1 ; Gholaminejad A2 ; Abolhassani H3, 4 ; Sherkate R5 ; Salehif M6 ; Sharifi M1
Authors
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Authors Affiliations
  1. 1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Regenerative Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
  4. 4. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Immunodeficiency Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  6. 6. Molecular and Genetics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Allergologia et Immunopathologia Published:2025


Abstract

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. © 2025 Codon Publications.
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