Identification and Analysis of Differentially Expressed Genes Associated with Ferroptosis an d HIV in PASMCs Based on Bioinformatics

Tong Lu; Linna Guo; Yong Ma; Lijie Yao; Li Li; Wenshan Bian; Miao Xiu; Yang Jiang; Yongtao Li; Haifeng Jin

doi:10.2174/011570162X304876240821062047

Identification and Analysis of Differentially Expressed Genes Associated with Ferroptosis an d HIV in PASMCs Based on Bioinformatics

Curr HIV Res. 2024 Aug 26. doi: 10.2174/011570162X304876240821062047. Online ahead of print.

Authors

Tong Lu¹, Linna Guo², Yong Ma², Lijie Yao², Li Li², Wenshan Bian², Miao Xiu², Yang Jiang², Yongtao Li², Haifeng Jin²

Affiliations

¹ College of Medical Technology, Qiqihar Medical University, Qiqihar, China.
² Department of Anatomy, Qiqihar Medical University, Qiqihar, China.

PMID: 39192637
DOI: 10.2174/011570162X304876240821062047

Abstract

Background: HIV-associated pulmonary arterial hypertension (HIV-PAH), a rare and fatal condition within the pulmonary arterial hypertension spectrum, is linked to HIV infection. While ferroptosis, an iron-dependent cell death form, is implicated in various lung diseases, its role in HIVPAH development remains unclear.

Methods: Leveraging Gene Expression Omnibus data, we identified differentially expressed genes (DEGs) in pulmonary arterial smooth muscle cells, including HIV-related DEGs (HIV-DEGs) and ferroptosis-related HIV-DEGs (FR-HIV-DEGs). PPI network analysis of FR-HIV-DEGs using CytoHubba in Cytoscape identified hub genes. We conducted functional and pathway enrichment analyses for FR-HIV-DEGs, HIV-DEGs, and hub genes. Diagnostic value assessment of hub genes utilized ROC curve analysis. Key genes were further screened, and external validation was performed. Additionally, we predicted a potential ceRNA regulatory network for key genes.

Results: 1372 DEGs were found, of which 228 were HIV-DEGs, and 20 were FR-HIV-DEGs. TP53, IL6, PTGS2, IL1B (downregulated), and PPARG (upregulated) were the five hub genes that were screened. TP53, IL6, and IL1B act as ferroptosis drivers, PTGS2 as a ferroptosis marker, and PPARG as a ferroptosis inhibitor. Enrichment analysis indicated biological processes enriched in "response to oxidative stress" and pathways enriched in "human cytomegalovirus infection." Key genes IL6 and PTGS2 exhibited strong predictive value via ROC curve analysis and external validation. The predicted ceRNA regulatory network identified miRNAs (has-mir-335-5p, has-mir-124-3p) targeting key genes and lncRNAs (XIST, NEAT1) targeting these miRNAs.

Conclusion: This study advances our understanding of potential mechanisms in HIV-PAH pathogenesis, emphasizing the involvement of ferroptosis. The findings offer valuable insights for future research in HIV-PAH.

Keywords: HIV; IL6; PTGS2.; ferroptosis; pulmonary arterial hypertension; pulmonary arterial smooth muscle cell.