Identification and validation of transcription factor-driven enhancers of genes related to lipid metabolism in metastatic oral squamous cell carcinomas.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35428233", "kind": "science-record", "revision": 5, "content_hash": "sha256:f7ee592dd272d9af022308037a05b8f5f06e1db9e4f558919967c386e4429ef7", "created_at": "2026-11-01T18:14:15Z", "updated_at": "2026-11-01T22:48:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of transcription factor-driven enhancers of genes related to lipid metabolism in metastatic oral squamous cell carcinomas.", "doi": "10.1186/s12903-022-02157-7", "pmid": "35428233", "authors": ["Liru Zhang", "Shuangling Zhao", "Yuanhang Liu", "Feifei Lv", "Xixue Geng"], "journal": "BMC oral health", "year": 2022, "abstract": "BACKGROUND: The role and mechanisms of lipid metabolism in oral squamous cell carcinomas (OSCC) metastasis have not been clarified. This study aims to identify lipid metabolism-related genes and transcription factors regulated by metastasis-associated enhancers (MAEs) in OSCC.\nMETHODS: Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed for lipid metabolism enrichment. TCGA data were used to analyze the differentially expressed lipid metabolism-related genes. MAEs were analyzed using GSE120634. Overlapping analysis was used to screen the MAE-regulated lipid metabolism-related genes, and the prognosis of these genes was analyzed. Transcription factor prediction was performed for the MAE-regulated lipid metabolism-related genes with prognostic value. Validation of the metastatic specificity of MAEs at ACAT1, OXSM and VAPA locus was performed using GSE88976 and GSE120634. ChIP-qPCR, qRT-PCR and Western blotting were used to verify the regulation of ACAT1, OXSM and VAPA expression by CBFB. Effects of CBFB knockdown on proliferation, invasion and lipid synthesis in metastatic OSCC cells were analyzed.\nRESULTS: Lipid metabolism was significantly enhanced in metastatic OSCC compared to non-metastatic OSCC. The expression of 276 lipid metabolism-related genes was significantly upregulated in metastatic OSCC, which were functionally related to lipid uptake, triacylglycerols, phospholipids and sterols metabolism. A total of 6782 MAEs and 176 MAE-regulated lipid metabolism-related genes were filtered. Three MAE-regulated lipid metabolism-related genes, ACAT1, OXSM and VAPA, were associated with a poor prognosis in OSCC patients. Enhancers at ACAT1, OXSM and VAPA locus were metastasis-specific enhancers. CBFB regulated ACAT1, OXSM and VAPA expression by binding to the enhancers of these genes. Knockdown of CBFB inhibited proliferation, invasion and lipid synthesis in metastatic OSCC cells.\nCONCLUSION: The MAE-regulated lipid metabolism-related genes (ACAT1, OXSM and VAPA) and the key transcription factor (CBFB) were identified. CBFB knockdown inhibited proliferation, invasion and lipid synthesis of OSCC cells. These findings provide novel candidates for the development of therapeutic targets for OSCC.", "claims": [{"id": "claim-method", "statement": "Differential expression analysis of lipid metabolism-related genes between metastatic OSCC and non-metastatic OSCC was carried out with data from TCGA database using the R package “limma”.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35428233", "locator": "sections[6] \"Identification and functional analysis of differentially expressed genes related to lipid metabolism\" paragraph 2", "quote": "Differential expression analysis of lipid metabolism-related genes between metastatic OSCC and non-metastatic OSCC was carried out with data from TCGA database using the R package “limma”."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analysed during the current study are available in the TCGA (https://tcga-data.nci.nih.gov/tcga/) and GEO (GSE120634 and GSE88976) repository.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35428233", "locator": "sections[32] \"notes\" paragraph 1", "quote": "The datasets generated and/or analysed during the current study are available in the TCGA (https://tcga-data.nci.nih.gov/tcga/) and GEO (GSE120634 and GSE88976) repository."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The expression of 276 lipid metabolism-related genes was significantly upregulated in metastatic OSCC, which were functionally related to lipid uptake, triacylglycerols, phospholipids and sterols metabolism.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35428233", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The expression of 276 lipid metabolism-related genes was significantly upregulated in metastatic OSCC, which were functionally related to lipid uptake, triacylglycerols, phospholipids and sterols metabolism."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The expression of 276 lipid metabolism-related genes was significantly upregulated in metastatic OSCC, which were functionally related to lipid uptake, triacylglycerols, phospholipids and sterols metabolism.", "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:35428233"], "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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ChIP-qPCR, qRT-PCR and Western blotting were used to v"], "order_basis": "paper_text_order:1033", "id": "assay:1"}, {"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": ["E88976 and GSE120634. ChIP-qPCR, qRT-PCR and Western blotting were used to verify the regulation of ACAT1,"], "order_basis": "paper_text_order:1051", "id": "assay:2"}, {"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": ["and VAPA expression by CBFB. Effects of CBFB knockdown on proliferation, invasion and lipid synthes", "by binding to the enhancers of these genes. Knockdown of CBFB inhibited proliferation, invasion an", "cription factor (CBFB) were identified. CBFB knockdown inhibited proliferation, invasion and lipid", "tascape.org/gp/index.html). Cell culture and transfection The human metastatic OSCC cells, HSC3 (JCRB"], "order_basis": "paper_text_order:1163", "id": "assay:3"}, {"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": ["and BHY (Cell Lines Service, Germany), were cultured in Dulbecco’s modified of Eagle medium (DMEM, G"], "order_basis": "paper_text_order:3197", "id": "assay:4"}, {"role": "data_generation", "definition_id": "chip_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["the MAE-regulated genes, we analyzed H3K27ac ChIP-seq data of HN120Met (metastatic OSCC cell line)"], "order_basis": "paper_text_order:6823", "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 lipid metabolism-related genes between metastatic OSCC and non-metastatic OSCC was carried out with data from TCGA database using the R package “limma”."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}