Transcription factor ASCL1 targets SLC6A13 to inhibit the progression of hepatocellular carcinoma via the glycine-inflammasome signaling.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38780447", "kind": "science-record", "revision": 4, "content_hash": "sha256:40387976e002c1551a43e3b06e17b7eb2c7618392a928f88eb6cd11fb6418099", "created_at": "2026-11-01T19:20:44Z", "updated_at": "2026-11-01T22:54:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Transcription factor ASCL1 targets SLC6A13 to inhibit the progression of hepatocellular carcinoma via the glycine-inflammasome signaling.", "doi": "10.17305/bb.2024.10328", "pmid": "38780447", "authors": ["Hongyan Zhang", "Ruiqing Zong", "Huiqi Wu", "Jun Jiang", "Chuanyong Liu", "Suiyi Liu"], "journal": "Biomolecules & biomedicine", "year": 2024, "abstract": "Hepatocellular carcinoma (HCC), the most common primary liver cancer, typically arises from chronic liver conditions such as hepatitis, cirrhosis, or other chronic liver diseases, and is characterized by its aggressive nature and poor prognosis. The purpose of this research was to clarify the function of achaete-scute family bHLH transcription factor 1 (ASCL1) and solute carrier family 6 member 13 (SLC6A13) in influencing tumor cell behavior, inflammatory responses, and the regulation of inflammasomes. We analyzed the differentially expressed genes (DEGs) in the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database, as well as in the GSE14520 and GSE67764 datasets, to identify the expression changes of SLC6A13 in liver cancer. The prognostic significance of SLC6A13 in LIHC was assessed through Kaplan-Meier survival curve analysis. Transcriptional regulation of SLC6A13 by ASCL1 was explored using the Joint Annotation of the Human Genome and other species by the Systematic Pipeline for the Annotation of Regulatory Regions (JASPAR) database and dual-luciferase assays. In vitro experiments investigated the impact of ASCL1 and SLC6A13 overexpression on HCC cell growth. Additionally, the effects of ethanol treatment and glycine modulation on the inflammatory response in HCC cell lines were evaluated. HCC samples showed reduced levels of SLC6A13, which correlates with a better prognosis for liver metastases. Elevated SLC6A13 expression correlated with improved overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-specific survival (DSS). ASCL1 upregulated SLC6A13 and inhibited proliferation, migration, and invasion of HCC cells. Ethanol induced the production of inflammatory cytokines, which was enhanced by overexpression of SLC6A13 but counteracted by glycine. This study highlighted elevated expression of SLC6A13 in LIHC which has been correlated with improved OS, PFS, RFS, and DSS. Overexpression of SLC6A13 and ASCL1 in HCC cells enhanced inflammasome activation, which was exacerbated by ethanol and attenuated by glycine.", "claims": [{"id": "claim-method", "statement": "The “limma” package from the R programming language was used to identify DEGs. A fold change (FC) threshold of >1.5 for upregulated genes and 0.67 for downregulated genes was used to evaluate statistical significance, using a minimum P value of less than 0.05 to assess statistical significance.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38780447", "locator": "sections[3] \"Dataset download and screening of differentially expressed genes (DEGs)\" paragraph 2", "quote": "The “limma” package from the R programming language was used to identify DEGs. A fold change (FC) threshold of >1.5 for upregulated genes and 0.67 for downregulated genes was used to evaluate statistical significance, using a minimum P value of less than 0.05 to assess statistical significance."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38780447", "locator": "sections[27] \"Data Availability\" paragraph 2", "quote": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "SLC6A13 expression was downregulated in tumor samples compared with normal samples in the TCGA-LIHC, GSE145290, and GSE67764 datasets.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38780447", "locator": "sections[16] \"Identification of DEGs and expression of SLC6A13 in liver cancer\" paragraph 2", "quote": "Expression analysis further showed that the expression of SLC6A13 was downregulated in tumor samples compared with normal samples in the TCGA-LIHC dataset (P ═ 1.1e−05), GSE145290 dataset, and GSE67764 dataset (Figure 1D–1F)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "SLC6A13 expression was downregulated in tumor samples compared with normal samples in the TCGA-LIHC, GSE145290, and GSE67764 datasets.", "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:38780447"], "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:GSE14520"], "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": {"fold_change": "y expressed genes, with fold-change thresholds and a minimu"}, "inputs": ["data:geo:GSE14520"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38780447", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": 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