Erkek İnfertilitesi ile İlgili MikroRNA'lara ve Hedef Genlere Biyoinformatik Yaklaşım

Yıl 2023, Cilt: 7 Sayı: 3, 296 - 303, 20.12.2023

Murat Kaya

https://doi.org/10.46332/aemj.1198311

Öz

Amaç: İnfertilite, dünya çapında çiftlerin yaklaşık %12'sini etkileyen bir sağlık sorunudur. İnfertilite oluşumunda erkek kaynaklı sorunların payı yaklaşık %50'dir. Birçok hücresel süreçte rol oynayan mikroRNA (miRNA)'lar, spermatogenez sürecinde de kritik rol üstlenmektedir. Anormal miRNA ifadesinin erkek fertilitesi üzerinde zararlı etkilerinin olduğu gösterilmiştir. İnfertilite ile ilişkili genlerdeki genetik değişikliklerin yanı sıra miRNA'lar gibi gen ekspresyonunu değiştiren epigenetik faktörlerin de infertilite sürecinde kuşkusuz rolü vardır. Bununla birlikte, infertilite ile ilgili genlerle hangi miRNA'ların ilişkili olduğu tam olarak bilinmemektedir. Bu çalışmanın amacı, çeşitli biyoinformatik araçlar kullanılarak infertilite ile ilişkili genlerin düzenlenmesinde rol oynayabilecek miRNA'ları belirlemektir.

Araçlar ve Yöntem: Çalışmada ilk önce Erkek İnfertilitesi Bilgi Bankası (MIK) veri tabanından infertilite ile ilişkili genler seçildi. Seçilen genlerin yolak analizi, bu genlerle ilgili protein-protein etkileşimi (PPI) ve hub proteinler, Elsevier pathway veri tabanı ve Enrichr aracı ile ortaya çıkarıldı. Ardından infertilite ile ilişkili genleri etkileyebilecek miRNA'lar belirlendi. Daha sonra miRNA-hedef gen ilişkisinin erkek infertilitesine etkisi miRPathDB 2.0 veritabanı, StarmiR ve miRNet gibi çeşitli in siliko araçlar kullanılmak suretiyle biyoinformatik olarak ortaya çıkarıldı.

Bulgular: MIK veri tabanından Erkek infertilitesi ile ilişkili 21 gen seçildi ve bu genlerin ifadesini biyoinformatik olarak düzenlemesi en muhtemel 15 miRNA belirlendi. Aynı zamanda seçilen erkek infertilite genleriyle ilişkili olabilecek 10 hub protein tespit edildi.

Sonuç: Biyoinformatik çalışma sonuçlarımız, miR-34a-5p ifade değişiminin CREM, LAMP3, AGBL5, FOXM1 genleri aracılığıyla ayrıca miR-335-5p'nin CFAP65, CFTR ve GAPDHS genleri üzerinden erkek infertilitesine neden olabileceğini göstermektedir.

Anahtar Kelimeler

Erkek İnfertilitesi, miR-335-5p, miR-34a-5p

Destekleyen Kurum

Herhangi bir kurumdan destek alınmamıştır

A Bioinformatics Approach to Male Infertility, MicroRNAs, and Targeted Genes

Öz

Purpose: Infertility affects nearly 12% of couples worldwide, with a male factor being the primary or contributory reason in around 50% of cases. MicroRNAs (miRNAs) are essential post-transcriptional regulators in the spermatogenesis process, and dysregulated miRNAs have been shown to have harmful effects on male fertility. However, it is unclear which miRNAs are associated with infertility-related genes. The aim of this study is, to identify miRNAs that may be involved in the regulation of infertility-related genes using various bioinformatics approaches.

Materials and Methods: The study first selected genes associated with infertility from the Male Infertility Knowledge Base (MIK) database. Pathway analysis of the defined genes, protein-protein interaction (PPI), and hub proteins related to these genes were revealed by the Elsevier pathway collection database and Enrichr tool. Following that, miRNAs that can influence infertility-related genes were determined, and the influence of the miRNA-target gene connection on male infertility was established bioinformatically using various in silico tools such as miRPathDB 2.0 tool, StarmiR, and miRNet.

Results: 21 male infertility associated genes were selected from the MIK database and 15 miRNAs that are most likely to regulate these genes were identified bioinformatically. 10 hub proteins related to defined male infertility genes were analyzed.

Conclusion: Our bioinformatic study results indicate that miR-34a-5p dysregulation may contribute to infertility through CREM, LAMP3, AGBL5, FOXM1 genes and also miR-335-5p may cause infertility via the CFAP65, CFTR, and GAPDHS genes.

Anahtar Kelimeler

Male infertility, miR-335-5p, miR-34a-5p

Kaynakça

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