Ferroptosis, an iron-dependent form of regulated cell death, has been associated with many virus infections. However, the role of ferroptosis in dengue virus (DENV) infection remains to be clarified. In our study, a dengue fever microarray dataset (GSE51808) of whole blood samples was downloaded from the Gene Expression Omnibus (GEO), and a list of ferroptosis related genes (FRGs) was extracted from the FerrDb. We identified 37 ferroptosis-related differentially expressed genes (FR-DEGs) in DENV-infected patient blood samples compared to healthy individuals. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses as well as protein–protein interaction (PPI) network of FR-DEGs revealed that these 37 FR-DEGs were mainly related to the C-type lectin receptor and p53 signaling pathway. Nine out of the 37 FR-DEGs (HSPA5, CAV1, HRAS, PTGS2, JUN, IL6, ATF3, XBP1, and CDKN2A) were hub genes, of which 5 were validated by qRT-PCR in DENV-infected HepG2 cells. Finally, using miRNA-mRNA regulatory network, we identified has-miR-124-3p and has-miR-16-5p as the most critical miRNAs in regulating the expression of these hub genes. In conclusion, our findings demonstrated that 5 FR-DEGs, JUN, IL6, ATF3, XBP1, and CDKN2A, and two miRNAs, has-miR-124-3p and has-miR-16-5p may implicate an essential role of ferroptosis in DENV infection, and further studies are warranted to explore the underlying mechanisms.
Supplementary Information
The online version contains supplementary material available at 10.1007/s11262-023-01985-1.