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Turkish Journal of Medical Sciences

Abstract

Background/aim: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF is characterized by respiratory tract infections, pancreatic insufficiency, meconium ileus, intestinal obstruction, and male infertility. A genotype to phenotype correlation is difficult to establish because of the heterogeneity of disease severity. Even patients with the same CFTR mutation can have varying clinical severities. In recent years, studies have explored the role of microRNA (miRNA) expression in the regulation of respiratory diseases. However, no research has been conducted to date on miRNAs in siblings with the same CFTR mutation.

Materials and methods: Nasal cells of CF siblings from two families with discordant phenotype (n = 2 per family) were collected, and differentially expressed miRNAs were identified using miRNA arrays. Differentially expressed miRNAs and their target genes were determined using several bioinformatic databases and tools.

Results: miR-449c-5p, miR-92b-3p, miR-34c-3p, miR-34c-5p, miR-6732-5p, and miR-4793-3p were differentially expressed in patients with severe disease compared to mild. CXCL1, CXCL2, DUSP1, GCLC, ICAM1, KIT, PRKAA2, and PTGS2 genes were identified as the target genes of candidate miRNAs (miR-34c-3p, miR-92b-3p, miR-449c-5p, miR-4793-3p). miRNA-mRNA interaction network analysis was performed and strong interaction was shown between miR-449c-5p target genes (CXCL1, CXCL2, PTGS2, ICAM1). CXCL1 expression decreased 5.28-fold in patients with severe disease compared to those with mild (p = 0.01).

Conclusion: Our results highlight the importance of miR-449c-5p interaction with CXCL1 and other target genes related to inflammation. Further studies should focus on the functional analysis of miR-449c-5p.

Author ORCID Identifier

AYBERK MUSTAFAOĞLU: 0009-0004-8538-1072

SENEM NOYAN: 0000-0001-6455-3702

YELİZ AKKAYA ULUM: 0000-0003-1888-2542

BALA GÜR DEDEOĞLU: 0000-0002-4320-5685

NAGEHAN EMİRALİOĞLU: 0000-0002-1405-8401

UĞUR ÖZÇELİK: 0000-0003-1587-5216

EBRU YALÇIN: 0000-0002-7325-1981

DENİZ DOĞRU: 0000-0001-9931-9473

NURAL KİPER: 0000-0003-1261-7393

DİDEM DAYANGAÇ ERDEN: 0000-0002-0236-7565

DOI

10.55730/1300-0144.6054

Keywords

Cystic fibrosis, genotype phenotype correlation, inflammation, miR-449c-5p, phenotypic variability

First Page

1014

Last Page

1023

Publisher

The Scientific and Technological Research Council of Türkiye (TÜBİTAK)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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