Epigenetic Regulation of MAP3K8 in EBV-Associated Gastric Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36768307", "kind": "science-record", "revision": 4, "content_hash": "sha256:67584a2210cf8fcae5154212218fe19d9875c687d6d45a7504af4fb6c5e66539", "created_at": "2026-11-01T19:01:21Z", "updated_at": "2026-11-01T22:51:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Epigenetic Regulation of MAP3K8 in EBV-Associated Gastric Carcinoma.", "doi": "10.3390/ijms24031964", "pmid": "36768307", "authors": ["Gaurab Roy", "Ting Yang", "Shangxin Liu", "Yi-Ling Luo", "Yuantao Liu", "Qian Zhong"], "journal": "International journal of molecular sciences", "year": 2023, "abstract": "Super-enhancers (SEs) regulate gene expressions, which are critical for cell type-identity and tumorigenesis. Although genome wide H3K27ac profiling have revealed the presence of SE-associated genes in gastric cancer (GC), their roles remain unclear. In this study, ChIP-seq and HiChIP-seq experiments revealed mitogen-activated protein kinase 8 (MAP3K8) to be an SE-associated gene with chromosome interactions in Epstein-Barr virus-associated gastric carcinoma (EBVaGC) cells. CRISPRi mediated repression of the MAP3K8 SEs attenuated MAP3K8 expression and EBVaGC cell proliferation. The results were validated by treating EBVaGC cells with bromodomain and the extra-terminal motif (BET) inhibitor, OTX015. Further, functional analysis of MAP3K8 in EBVaGC revealed that silencing MAP3K8 could inhibit the cell proliferation, colony formation, and migration of EBVaGC cells. RNA-seq and pathway analysis indicated that knocking down MAP3K8 obstructed the notch signaling pathway and epithelial-mesenchymal transition (EMT) in EBVaGC cells. Further, analysis of the cancer genome atlas (TCGA) and GSE51575 databases exhibited augmented MAP3K8 expression in gastric cancer and it was found to be inversely correlated with the disease-free progression of GC. Moreover, Spearman's correlation revealed that MAP3K8 expression was positively correlated with the expressions of notch pathway and EMT related genes, such as, Notch1, Notch2, C-terminal binding protein 2 (CTBP2), alpha smooth muscle actin isotype 2 (ACTA2), transforming growth factor beta receptor 1 (TGFβR1), and snail family transcriptional repressors 1/2 (SNAI1/SNAI2) in GC. Taken together, we are the first to functionally interrogate the mechanism of SE-mediated regulation of MAP3K8 in EBVaGC cell lines.", "claims": [{"id": "claim-method", "statement": "An unpaired parametric t-test with Welch correction and a two-way ANOVA with Geisser–Greenhouse correction were used to determine the statistical significance between the groups and values of p ≤ 0.05 were considered significant.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36768307", "locator": "sections[25] \"4.16. 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Source data are provided with this paper.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36768307", "locator": "sections[32] \"notes\" paragraph 1", "quote": "Data Availability StatementThe raw sequencing data reported in this paper have been deposited in the Genome Sequence Archive of the BIG Data Center at the Beijing Institute of Genomics, Chinese Academy of Science, under accession number HRA002658, accessible at https://ngdc.cncb.ac.cn/gsub/ (accessed on 11 January 2023). The authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform (www.researchdata.org.cn), with the approval number as RDDB2023766851. Source data are provided with this paper."}], "state": "complete"}, {"id": "claim-target-result", "statement": "CRISPRi mediated repression of the MAP3K8 SEs attenuated MAP3K8 expression and EBVaGC cell proliferation.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36768307", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "CRISPRi mediated repression of the MAP3K8 SEs attenuated MAP3K8 expression and EBVaGC cell proliferation."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "CRISPRi mediated repression of the MAP3K8 SEs attenuated MAP3K8 expression and EBVaGC cell proliferation.", "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:36768307"], "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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