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pmid:36819785

The Effect of N6-Methyladenosine Regulators and m6A Reader YTHDC1-Mediated N6-Methyladenosine Modification Is Involved in Oxidative Stress in Human Aortic Dissection.

Fanxing Yin · Kun Liu · Wanfu Peng · Deying Jiang · Hao Zhang · Panpan Guo · Yinhao Wu · Xiaoxu Zhang · Chenxi Sun · Yaxuan Wang · Hecheng Wang · Yanshuo Han

Oxidative medicine and cellular longevity · 2023 doi:10.1155/2023/3918393

Paper

complete

Experiment

complete

Data

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Analysis

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Execution

absent

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title
The Effect of N6-Methyladenosine Regulators and m6A Reader YTHDC1-Mediated N6-Methyladenosine Modification Is Involved in Oxidative Stress in Human Aortic Dissection.
doi
10.1155/2023/3918393
pmid
36819785
authors array · 12 items
[0]
Fanxing Yin
[1]
Kun Liu
[2]
Wanfu Peng
[3]
Deying Jiang
[4]
Hao Zhang
[5]
Panpan Guo
[6]
Yinhao Wu
[7]
Xiaoxu Zhang
[8]
Chenxi Sun
[9]
Yaxuan Wang
[10]
Hecheng Wang
[11]
Yanshuo Han
journal
Oxidative medicine and cellular longevity
year
2023
abstract
Aortic dissection (AD) develops pathological changes in the separation of the true and false aortic lumen, with high lethality. m6A methylation and oxidative stress have also been shown to be involved in the onset of AD. Through bioinformatics methods, three differentially expressed m6A regulators (YTHDC1, YTHDC2, and RBM15) were excavated from the GSE52093 dataset in the Gene Expression Omnibus (GEO) database, and functional enrichment analysis of the differentially expressed genes (DEGs) regulated by m6A regulators was performed. Then, the genes with oxidative stress-related functions among these genes were found. The protein interaction network of the oxidative stress-related genes and the competing endogenous RNA- (ceRNA-) miRNA-mRNA network were constructed. Among them, DHCR24, P4HB, and PDGFRA, which have m6A differences in AD samples, were selected as key genes. We also performed immune infiltration analysis, as well as cell-gene correlation analysis, on samples from the dataset. The results showed that YTHDC1 was positively correlated with macrophage M1 and negatively correlated with macrophage M2. Finally, we extracted AD and healthy aorta RNA and protein from human tissues that were taken from AD patients and patients who received heart transplants, performed quantitative real-time PCR (qRT-PCR) on YTHDC2 and RBM15, and performed qRT-PCR and western blot (WB) detection on YTHDC1 to verify their differences in AD. The mRNA and protein levels of YTHDC1 were consistent with the results of bioinformatics analysis and were downregulated in AD. Immunofluorescence (IF) was used to colocalize YTHDC1 and endothelial cell marker CD31. After knocking down YTHDC1 in human umbilical vein endothelial cells (HUVECs), reactive oxygen species (ROS) levels had a tendency to increase and the expression of peroxide dismutase SOD2 was decreased. This study provides assistance in discovering the role of m6A regulator YTHDC1 in AD. In particular, m6A modification participates in oxidative stress and jointly affects AD.
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sections[3] "2.1. Data Collection and Screening of Differentially Expressed m6A Regulatory Genes" paragraph 2
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Differential expression analysis of genes between AD and normal aorta was performed by using the R software package “limma.”
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Through the screening of differential expression, we finally obtained three m6A regulators (YTHDC1, YTHDC2, and RBM15) as DEMRGs.
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sections[16] "3.1. Identification of Differentially Expressed m6A Regulatory Genes" paragraph 2
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Through the screening of differential expression, we finally obtained three m6A regulators (YTHDC1, YTHDC2, and RBM15) as DEMRGs.
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Through the screening of differential expression, we finally obtained three m6A regulators (YTHDC1, YTHDC2, and RBM15) as DEMRGs.
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ed heart transplants, performed quantitative real-time PCR (qRT-PCR) on YTHDC2 and RBM15, and performed
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YTHDC2 and RBM15, and performed qRT-PCR and western blot (WB) detection on YTHDC1 to verify their dif
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atics analysis and were downregulated in AD. Immunofluorescence (IF) was used to colocalize YTHDC1 and endot
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2. Endothelial Cell Culture and YTHDC1 siRNA Transfection HUVECs were cultured with complete growth me
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36819785", "kind": "science-record", "revision": 4, "content_hash": "sha256:ee33d780411acd0ce6f164d74bf62a0f665a28c8d47107b220d342eb41cc25dc", "created_at": "2026-11-01T19:01:25Z", "updated_at": "2026-11-01T22:51:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The Effect of N6-Methyladenosine Regulators and m6A Reader YTHDC1-Mediated N6-Methyladenosine Modification Is Involved in Oxidative Stress in Human Aortic Dissection.", "doi": "10.1155/2023/3918393", "pmid": "36819785", "authors": ["Fanxing Yin", "Kun Liu", "Wanfu Peng", "Deying Jiang", "Hao Zhang", "Panpan Guo", "Yinhao Wu", "Xiaoxu Zhang", "Chenxi Sun", "Yaxuan Wang", "Hecheng Wang", "Yanshuo Han"], "journal": "Oxidative medicine and cellular longevity", "year": 2023, "abstract": "Aortic dissection (AD) develops pathological changes in the separation of the true and false aortic lumen, with high lethality. m6A methylation and oxidative stress have also been shown to be involved in the onset of AD. Through bioinformatics methods, three differentially expressed m6A regulators (YTHDC1, YTHDC2, and RBM15) were excavated from the GSE52093 dataset in the Gene Expression Omnibus (GEO) database, and functional enrichment analysis of the differentially expressed genes (DEGs) regulated by m6A regulators was performed. Then, the genes with oxidative stress-related functions among these genes were found. The protein interaction network of the oxidative stress-related genes and the competing endogenous RNA- (ceRNA-) miRNA-mRNA network were constructed. Among them, DHCR24, P4HB, and PDGFRA, which have m6A differences in AD samples, were selected as key genes. We also performed immune infiltration analysis, as well as cell-gene correlation analysis, on samples from the dataset. The results showed that YTHDC1 was positively correlated with macrophage M1 and negatively correlated with macrophage M2. Finally, we extracted AD and healthy aorta RNA and protein from human tissues that were taken from AD patients and patients who received heart transplants, performed quantitative real-time PCR (qRT-PCR) on YTHDC2 and RBM15, and performed qRT-PCR and western blot (WB) detection on YTHDC1 to verify their differences in AD. The mRNA and protein levels of YTHDC1 were consistent with the results of bioinformatics analysis and were downregulated in AD. Immunofluorescence (IF) was used to colocalize YTHDC1 and endothelial cell marker CD31. After knocking down YTHDC1 in human umbilical vein endothelial cells (HUVECs), reactive oxygen species (ROS) levels had a tendency to increase and the expression of peroxide dismutase SOD2 was decreased. This study provides assistance in discovering the role of m6A regulator YTHDC1 in AD. In particular, m6A modification participates in oxidative stress and jointly affects AD.", "claims": [{"id": "claim-method", "statement": "Differential expression analysis of genes between AD and normal aorta was performed by using the R software package “limma.”", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36819785", "locator": "sections[3] \"2.1. Data Collection and Screening of Differentially Expressed m6A Regulatory Genes\" paragraph 2", "quote": "Differential expression analysis of genes between AD and normal aorta was performed by using the R software package “limma.”"}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used or analyzed during the current study are available from the corresponding author on reasonable request. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36819785", "locator": "sections[28] \"Data Availability\" paragraph 2", "quote": "The datasets used or analyzed during the current study are available from the corresponding author on reasonable request. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Through the screening of differential expression, we finally obtained three m6A regulators (YTHDC1, YTHDC2, and RBM15) as DEMRGs.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36819785", "locator": "sections[16] \"3.1. Identification of Differentially Expressed m6A Regulatory Genes\" paragraph 2", "quote": "Through the screening of differential expression, we finally obtained three m6A regulators (YTHDC1, YTHDC2, and RBM15) as DEMRGs."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Through the screening of differential expression, we finally obtained three m6A regulators (YTHDC1, YTHDC2, and RBM15) as DEMRGs.", "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:36819785"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE147027"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE147027"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36819785", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2023/3918393", "sha256": "sha256:dcc1f0fdb497ad227043dcae97fa65e5160b387717d81c9d4c0cc68b80386fa1", "bytes": 38322, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2023/3918393", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9935809", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE147027", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE147027", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE147027", "version": null, "note": "The datasets used or analyzed during the current study are available from the corresponding author on reasonable request. 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The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4644214", "GSM4644215", "GSM4644216", "GSM4644217", "GSM4644218", "GSM4644219", "GSM4644220", "GSM4644221", "GSM4644222", "GSM4644223", "GSM4644224", "GSM4644225", "GSM4644226", "GSM4644227", "GSM4644228", "GSM4644229", "GSM4644230", "GSM4644231", "GSM4644232", "GSM4644233"], "sample_count": 20, "group_sizes": null, "group_sizes_basis": null, "platform": "20795", "taxon": "Homo sapiens", "title": "Exaggerated autophagy as molecular characterization of Stanford type A aortic dissection: A transcriptome analysis of human ascending aortic tissues", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE52093", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52093", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE52093", "version": null, "note": "The datasets used or analyzed during the current study are available from the corresponding author on reasonable request. 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Immunofluorescence (IF) was used to colocalize YTHDC1 and endot"], "order_basis": "paper_text_order:1697", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["2. Endothelial Cell Culture and YTHDC1 siRNA Transfection HUVECs were cultured with complete growth me", "on of 30%. After cell spreading, HUVECs were transfected with 75 nM YTHDC1 siRNAs or NC siRNAs for 48", "siRNAs or NC siRNAs for 48 h by riboFECT™ CP Transfection Kit (C10511-05, RiboBio, Guangzhou, China).", "s. Then, total RNA was extracted after siRNA transfection, for further qRT-PCR analysis of transfectio"], "order_basis": "paper_text_order:5050", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["re and YTHDC1 siRNA Transfection HUVECs were cultured with complete growth medium DMEM High Glucose (MA"], "order_basis": "paper_text_order:5081", "id": "assay:5"}, {"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": ["Differential expression analysis of genes between AD and normal aorta was performed by using the R software package “limma.”"], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}