RNA ve protein seviyelerinde temel biyobelirteçleri belirlemek için pulmoner arteriyel hipertansiyonun in silico analizi

Yıl 2023, Cilt: 11 Sayı: 4, 2053 - 2067, 24.10.2023

Sevinç Akçay

https://doi.org/10.29130/dubited.1103902

Öz

Pulmoner arteriyel hipertansiyon (PAH), pulmoner arterlerde yüksek hipertansiyon ile işaretlenmiş kronik bir kardiyopulmoner bozukluktur. PAH için bir tam bir tedavi yoktur, mevcut ilaçlar hastalığın ilerlemesini azaltmaya yardımcı olabilir. Bu araştırma, biyoinformatik analiz yoluyla PAH'ın potansiyel protein ve RNA biyobelirteçlerini araştırmayı amaçlamıştır. Herkese açık Gene Expression Omnibus (GEO) veri tabanından erişilen iki PAH veri seti, diferansiyel olarak eksprese edilmiş genleri (DEG'ler) keşfetmek için kullanıldı. Yaygın DEG'ler için Gen Ontology (GO) ve Kyoto Genler ve Genler Ansiklopedisi (KEGG) yolsk analizleri DAVID aracıyla yapıldı. Cytoscape, protein-protein etkileşimini (PPI) oluşturmak ve ilk 10 hub genini seçmek için kullanıldı. DEG'leri ve hub genlerini hedefleyen transkripsiyon faktörleri (TF'ler) ve mikroRNA'lar (miRNA'lar), JASPAR veri tabanı kullanılarak araştırıldı. En iyi hub genlerini hedef alan potansiyel terapötikler keşfedildi. On hub geninin PAH patogeneziyle bağlantılı olduğu keşfedildi (CCL5, TLR4, TLR1, SPP1, CYBB, HGF, IGF1, SELL, CD163 ve POSTN). “Tümör nekroz faktörü biyosentetik sürecinin pozitif regülasyonu” ve “ücret benzeri reseptör sinyal yolu” sırasıyla en zenginleştirilmiş GO terimi ve KEGG yoludur. “hsa-mir-26b-5p, hsa-mir-146a-5p, hsa-mir-335-5p” ve FOXC1, YY1, GATA2, hub genlerini hedefleyen en iyi TF'lerdir. On hub genini hedef alan 21 ilaç keşfedildi. Sonuçlarımız, PAH hastaları için protein ve RNA seviyelerinde potansiyel terapötik hedefler olarak hizmet edebilecek PAH ve hub genleri, miRNA'lar ve 10 TF'nin patogenezini keşfetmeye yardımcı olacaktır.

Anahtar Kelimeler

Pulmoner arteryel hipertansiyon, Biyobelirteçler, Transkripsiyon faktörleri, MikroRNAlar, Diferansiyel olarak eksprese edilen genler

In silico analysis of pulmonary arterial hypertension to identify key biomarkers at protein and RNA levels

Öz

Pulmonary arterial hypertension (PAH) is a chronic cardiopulmonary disorder marked by a raised hypertension in the pulmonary arteries. There is no remedy for PAH, existing medications can help reduce the disease’s progression. This research aimed to investigate potential protein and RNA biomarkers of PAH by bioinformatic analysis. Two PAH datasets accessed from the publicly available Gene Expression Omnibus (GEO) database were used to discover differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for common DEGs were conducted by the DAVID tool. Cytoscape was used to create the protein-protein interaction (PPI) and pick the top 10 hub genes. The transcription factors (TFs) and microRNAs (miRNAs) that target DEGs and hub genes were investigated using the JASPAR database. Potential therapeutics that target the top hub genes have been discovered. Ten hub genes were discovered to be linked to the pathogenesis of PAH (CCL5, TLR4, TLR1, SPP1, CYBB, HGF, IGF1, SELL, CD163, and POSTN). “Positive regulation of tumor necrosis factor biosynthetic process” and a “toll-like receptor signaling pathway” are the most enriched GO term and KEGG pathway, respectively. “hsa-mir-26b-5p, hsa-mir-146a-5p, hsa-mir-335-5p” and FOXC1, YY1, GATA2 are the top TFs targeting hub genes. 21 drugs targeting ten hub genes have been discovered. Our results would help to discover the pathogenesis of PAH and hub genes, miRNAs and 10 TFs that might serve as potential therapeutic targets at protein and RNA levels for PAH patients.

Anahtar Kelimeler

Pulmonary arterial hypertension, Biomarkers, Transcription factors, MicroRNAs, Differentially expressed genes

Kaynakça

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