RNA ve protein seviyelerinde temel biyobelirteçleri belirlemek için pulmoner arteriyel hipertansiyonun in silico analizi
Affiliation:
1. AHİ EVRAN ÜNİVERSİTESİ
Abstract
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.
Publisher
Duzce Universitesi Bilim ve Teknoloji Dergisi
Reference37 articles.
1. [1] Tuder RM, Archer SL, Dorfmuller P, Erzurum SC, Guignabert C, Michelakis E, Rabinovitch M, Schermuly R, Stenmark KR, Morrell NW, “Relevant issues in the pathology and pathobiology of pulmonary hypertension, ” J Am Coll Cardiol, 62(25 Suppl):D4–12, 2013. 2. [2] Simonneau G, Montani D, Celermajer DS, et al., “Haemodynamic definitions and updated clinical classification of pulmonary hypertension, ” Eur Respir, 53(1), 2019. 3. [3] Edgar R, Domrachev M, Lash AE., Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res, 30(1):207-10, 2002. 4. [4] Mi, , Muruganujan, A, and Thomas, P, “PANTHER in Modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees,” Nucleic Acids Res,. 41(Database issue), D377-386, 2013.
[5] Huang DW, Sherman BT, Lempicki RA, “Systematic and integrative analysis of large gene lists using DAVID Bioinformatics Resource,” Nature Protoc, 4(1):44-57, 2009. 5. [6] Warde-Farley, D, Donaldson, S. L, Comes, O, Zuberi, K, Badrawi, R, Chao, P, Franz, M, Grouios, C, Kazi, F, F, Lopes, C T, Maitland, A, Mostafavi, S, Montojo, J, Shao, Q, Wright, G, Bader, G D, & Morris, Q, “The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function,” Nucleic acids research 38(Web Server issue), W214–W220, 2010.
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