YTHDC1 Regulates the Migration, Invasion, Proliferation, and Apoptosis of Rheumatoid Fibroblast-Like Synoviocytes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39534605", "kind": "science-record", "revision": 4, "content_hash": "sha256:fe0a132f389e2d2602e9297ecf4bde509badb66787662ac79673eaec191b6e2d", "created_at": "2026-11-01T20:29:48Z", "updated_at": "2026-11-01T22:55:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "YTHDC1 Regulates the Migration, Invasion, Proliferation, and Apoptosis of Rheumatoid Fibroblast-Like Synoviocytes.", "doi": "10.3389/fimmu.2024.1440398", "pmid": "39534605", "authors": ["Zhi-Wei Feng", "Chen-Fei Yang", "He-Fang Xiao", "Fa Yuan", "Feng Chen", "Bo Zhang", "Jun Zhang", "Min Tan", "Ming-Gang Guo"], "journal": "Frontiers in immunology", "year": 2024, "abstract": "Background: Rheumatoid arthritis (RA), a chronic autoimmune condition, is characterized by persistent synovial inflammation, bone degradation, and progressive joint deterioration. Despite considerable research efforts, the precise molecular mechanism underlying RA remains elusive. This investigation aims to elucidate the potential role and molecular mechanism of N6-methyladenosine (m6A) methylation regulators in the pathogenesis of RA.\nMethods: In this study, we employed bioinformatics tools to elucidate the association between RA and m6A modifications, aiming to identify potential biological markers. We extracted datasets GSE12021, GSE55235, and GSE55457 from the Gene Expression Omnibus (GEO) database for comprehensive analysis. Utilizing differential expression analysis, protein-protein interaction (PPI) analysis, and single-cell sequencing techniques, we identified pivotal hub genes implicated in the pathogenesis of RA. Subsequently, we assessed the correlation between these hub genes and the pathogenesis of RA using Gene Set Enrichment Analysis (GSEA). Both in vivo and in vitro experiments were performed to confirm the expression and functional roles of the identified key hub gene in RA.\nResults: Differential expression analysis, PPI analysis, and single-cell analysis identified three key hub genes (YTHDC1, YTHDC2, and YTHDF2) associated with RA. GSEA results further revealed that these genes are enriched in pathways associated with inflammatory responses. Subsequent correlation analysis demonstrated a significant negative correlation between YTHDC1 expression and CD8+ T cell levels. Notably, the gene and protein expression levels of YTHDC1 and YTHDF2 were significantly reduced in the synovial tissue of RA patients. Furthermore, silencing YTHDC1 in fibroblast-like synoviocytes (FLSs) significantly inhibited their migration, invasion, proliferation, and induced apoptosis.\nConclusion: YTHDC1 may potentially be involved in the pathogenesis of RA through its regulation of migration, invasion, proliferation, and apoptosis in FLSs.", "claims": [{"id": "claim-method", "statement": "The “Limma” package (38) was used to identify differentially expressed genes (DEGs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39534605", "locator": "sections[3] \"Data processing and differential expression analysis\" paragraph 3", "quote": "The “Limma” package (38) was used to identify differentially expressed genes (DEGs)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets supporting the conclusions of this article are available in the NCBI GEO repository, accession numbers GSE12021, GSE55235, GSE55457, GSE159117. The experimental data used in this study are available from the corresponding author upon a reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39534605", "locator": "sections[34] \"Data availability statement\" paragraph 2", "quote": "The datasets supporting the conclusions of this article are available in the NCBI GEO repository, accession numbers GSE12021, GSE55235, GSE55457, GSE159117. The experimental data used in this study are available from the corresponding author upon a reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "YTHDC1 may potentially be involved in the pathogenesis of RA through its regulation of migration, invasion, proliferation, and apoptosis in FLSs.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39534605", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "YTHDC1 may potentially be involved in the pathogenesis of RA through its regulation of migration, invasion, proliferation, and apoptosis in FLSs."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "YTHDC1 may potentially be involved in the pathogenesis of RA through its regulation of migration, invasion, proliferation, and apoptosis in FLSs.", "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:39534605"], "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:GSE12021"], "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:GSE12021"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39534605", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2024.1440398", "sha256": "sha256:9e3e4168adb8b7c3ca2337cace2c26a1ca003a8dbb3f3a23779f13673871467f", "bytes": 58461, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2024.1440398", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11554466", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE12021", "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=GSE12021", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE12021", "version": null, "note": "The datasets supporting the conclusions of this article are available in the NCBI GEO repository, accession numbers GSE12021, GSE55235, GSE55457, GSE159117. 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Conclusion: YTHDC1 may potentially be invol", "n of migration, invasion, proliferation, and apoptosis in FLSs."], "order_basis": "paper_text_order:17", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ng Gene Set Enrichment Analysis (GSEA). 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Quantitative real-time PCR (QRT-PCR) and Western blot analyses revealed"], "order_basis": "paper_text_order:6698", "id": "assay:4"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["). Quantitative real-time PCR (QRT-PCR) and Western blot analyses revealed a reduction in YTHDC1 and"], "order_basis": "paper_text_order:6727", "id": "assay:5"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["statistically significant ( Figures 5D, E ). IHC and IF analyses further confirmed the downre", "and YTHDF2 in TC and RA samples (n = 3). 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