Bioinformatics Analysis Confirms Potential Necroptosis Genes in the Pathogenesis of Pulmonary Artery Hypertension
1. Cardiovascular Research Center, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center
2. Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an 710061, China
| Abstract: | Objective: Pulmonary artery hypertension (PAH) is a life-threatening lung disease without effective therapeutic agents. Necroptosis plays a key role in the pathogenesis of PAH. We therefore investigated to identify and validate the potential necroptosis-related genes in PAH by bioinformatics analysis and experiments. Methods: Firstly, the microarray data of PAH (GSE15197) and necroptosis-related genes were obtained from Gene Expression Omnibus (GEO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Then we used the bioinformatics methods to identify the differentially expressed genes (DEGs) between the normal lungs and the lungs of PAH patients and extract the necroptosis-related DEGs. Enrichment analysis and protein-protein interaction (PPI) analysis were performed to screen the hub genes. Module construction and co-expression analysis of hub genes were also conducted. Key transcription factors (TFs) of hub genes were obtained by using the TRRUST website. Finally, the experimental mouse PAH model was performed to verify the expression of hub genes and key TFs by qRT-PCR. Results: A total of 16 necroptosis-related DEGs (10 upregulated genes and 6 downregulated genes) were identified by comparing the normal lungs and the lungs of PAH patients. ClueGO and KEGG enrichment analysis demonstrated these necroptosis-related DEGs were involved in positive regulation of nitric oxide biosynthetic process, programmed necrotic cell death, positive regulation of chemokine production, necroptosis, and NOD-like receptor signaling pathway. 7 hub genes were obtained by cytoHubba, including BAX, XIAP, TLR4, TNF, HSP90AA1, FAS, and TNFSF10. qRT-PCR analysis confirmed that expression of Bax, Tlr4, Tnf, Hsp90aa1, Fas and Tnfsf10 were significantly upregulated, while the expression level of Xiap was not significant in mouse lungs with experimental PAH compared with normal mouse lungs. Conclusion: Our study identified 7 important hub genes related to necroptosis in PAH, which could be used as potential therapeutic targets and provide new insights into further mechanism study for PAH. |
| Keywords: | Necroptosis; Pulmonary Artery Hypertension; Bioinformatics Analysis; Gene Expression Omnibus; Hub Genes; Transcription Factors |
| DOI: | 10.57237/j.life.2024.01.003 |
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Received: 7 December 2023
Accepted: 24 January 2024
Published Online: 4 February 2024
Funding
| 1. | 国家自然科学基金项目 (82000072) |
| 2. | 中国博士后科学基金项目 (2020M673425) |
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