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pmid:36973608

Identification and validation of ferroptosis-related genes in patients infected with dengue virus: implication in the pathogenesis of DENV.

Jinlian Li · Xipeng Yan · Bin Li · Linbing Huang · Xinwei Wang · Baoren He · He Xie · Qunying Wu · Limin Chen

Virus genes · 2023 doi:10.1007/s11262-023-01985-1

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
Identification and validation of ferroptosis-related genes in patients infected with dengue virus: implication in the pathogenesis of DENV.
doi
10.1007/s11262-023-01985-1
pmid
36973608
authors array · 9 items
[0]
Jinlian Li
[1]
Xipeng Yan
[2]
Bin Li
[3]
Linbing Huang
[4]
Xinwei Wang
[5]
Baoren He
[6]
He Xie
[7]
Qunying Wu
[8]
Limin Chen
journal
Virus genes
year
2023
abstract
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.
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DEGs between patients with DENV infection and the healthy individuals were identified using the DESeq2 package in R software with cutoffs at |log2 FC|> 1 and P-value < 0.05 [16].
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DEGs between patients with DENV infection and the healthy individuals were identified using the DESeq2 package in R software with cutoffs at |log2 FC|> 1 and P-value < 0.05 [16].
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The datasets supporting the conclusions of this article are available in the Gene Expression Omnibus (GEO) (www.ncbi.nlm.nih.gov/geo) database and the FerrDB (http://www.zhounan.org/ferrdb/current/) database.
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The datasets supporting the conclusions of this article are available in the Gene Expression Omnibus (GEO) (www.ncbi.nlm.nih.gov/geo) database and the FerrDB (http://www.zhounan.org/ferrdb/current/) database.
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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.
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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.
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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.
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Complete file
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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.", "claims": [{"id": "claim-method", "statement": "DEGs between patients with DENV infection and the healthy individuals were identified using the DESeq2 package in R software with cutoffs at |log2 FC|> 1 and P-value < 0.05 [16].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36973608", "locator": "sections[4] \"Screening of FR-DEGs from DENV-infected whole blood samples\" paragraph 2", "quote": "DEGs between patients with DENV infection and the healthy individuals were identified using the DESeq2 package in R software with cutoffs at |log2 FC|> 1 and P-value < 0.05 [16]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets supporting the conclusions of this article are available in the Gene Expression Omnibus (GEO) (www.ncbi.nlm.nih.gov/geo) database and the FerrDB (http://www.zhounan.org/ferrdb/current/) database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36973608", "locator": "sections[24] \"Data availability\" paragraph 2", "quote": "The datasets supporting the conclusions of this article are available in the Gene Expression Omnibus (GEO) (www.ncbi.nlm.nih.gov/geo) database and the FerrDB (http://www.zhounan.org/ferrdb/current/) database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "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.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36973608", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "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."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "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.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36973608"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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HepG2 cells were infected with DENV-2 in a multipl"], "order_basis": "paper_text_order:1077", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["e, C-type lectin receptor signaling pathway, apoptosis, and p53 signaling pathway (Fig. 3B). The to"], "order_basis": "paper_text_order:4472", "id": "assay:3"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["DEGs between patients with DENV infection and the healthy individuals were identified using the DESeq2 package in R software with cutoffs at |log2 FC|> 1 and P-value < 0.05 [16]."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}