Title:Identification and Analysis of Differentially Expressed Genes Associated with Ferroptosis and HIV in PASMCs Based on Bioinformatics
Volume: 22
Issue: 5
Author(s): Tong Lu, Linna Guo, Yong Ma, Lijie Yao, Li Li, Wenshan Bian, Miao Xiu, Yang Jiang*, Yongtao Li*Haifeng Jin*
Affiliation:
- Department of Anatomy, Qiqihar
Medical University, Qiqihar, China
- Department of Anatomy, Qiqihar
Medical University, Qiqihar, China
- Department of Anatomy, Qiqihar
Medical University, Qiqihar, China
Keywords:
HIV, pulmonary arterial hypertension, ferroptosis, pulmonary arterial smooth muscle cell, IL6, PTGS2.
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.
