Nuclear respiratory factor 1 regulates super enhancer-controlled SPIDR to protect hepatocellular carcinoma cells from oxidative stress.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38438958", "kind": "science-record", "revision": 4, "content_hash": "sha256:e0587677454d209bd5a3e8fbcce6753a38e138b9f0a89d88ded90aa8d1c47eba", "created_at": "2026-11-01T19:20:22Z", "updated_at": "2026-11-01T22:53:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Nuclear respiratory factor 1 regulates super enhancer-controlled SPIDR to protect hepatocellular carcinoma cells from oxidative stress.", "doi": "10.1186/s12876-024-03183-1", "pmid": "38438958", "authors": ["Baowang Liu", "Jian Dou", "Jinglin Cao"], "journal": "BMC gastroenterology", "year": 2024, "abstract": "BACKGROUND: Cellular response to oxidative stress plays significant roles in hepatocellular carcinoma (HCC) development, yet the exact mechanism by which HCC cells respond to oxidative stress remains poorly understood. This study aimed to investigate the role and mechanism of super enhancer (SE)-controlled genes in oxidative stress response of HCC cells.\nMETHODS: The GSE112221 dataset was used to identify SEs by HOMER. Functional enrichment of SE-controlled genes was performed by Metascape. Transcription factors were predicted using HOMER. Prognosis analysis was conducted using the Kaplan-Meier Plotter website. Expression correlation analysis was performed using the Tumor Immune Estimation Resource web server. NRF1 and SPIDR expression in HCC and normal liver tissues was analyzed based on the TCGA-LIHC dataset. ChIP-qPCR was used to detect acetylation of lysine 27 on histone 3 (H3K27ac) levels of SE regions of genes, and the binding of NRF1 to the SE of SPIDR. To mimic oxidative stress, HepG2 and Hep3B cells were stimulated with H2O2. The effects of NRF1 and SPIDR on the oxidative stress response of HCC cells were determined by the functional assays.\nRESULTS: A total of 318 HCC-specific SE-controlled genes were identified. The functions of these genes was significant association with oxidative stress response. SPIDR and RHOB were enriched in the \"response to oxidative stress\" term and were chosen for validation. SE regions of SPIDR and RHOB exhibited strong H3K27ac modification, which was significantly inhibited by JQ1. JQ1 treatment suppressed the expression of SPIDR and RHOB, and increased reactive oxygen species (ROS) levels in HCC cells. TEAD2, TEAD3, NRF1, HINFP and TCFL5 were identified as potential transcription factors for HCC-specific SE-controlled genes related to oxidative stress response. The five transcription factors were positively correlated with SPIDR expression, with the highest correlation coefficient for NRF1. NRF1 and SPIDR expression was up-regulated in HCC tissues and cells. NRF1 activated SPIDR transcription by binding to its SE. Silencing SPIDR or NRF1 significantly promoted ROS accumulation in HCC cells. Under oxidative stress, silencing SPIDR or NRF1 increased ROS, malondialdehyde (MDA) and γH2AX levels, and decreased superoxide dismutase (SOD) levels and cell proliferation of HCC cells. Furthermore, overexpression of SPIDR partially offset the effects of NRF1 silencing on ROS, MDA, SOD, γH2AX levels and cell proliferation of HCC cells.\nCONCLUSION: NRF1 driven SPIDR transcription by occupying its SE, protecting HCC cells from oxidative stress-induced damage. NRF1 and SPIDR are promising biomarkers for targeting oxidative stress in the treatment of HCC.", "claims": [{"id": "claim-method", "statement": "Comparisons among more than two groups were performed using one-way analysis of variance (ANOVA) with Tukey’s post hoc test. Comparisons between two groups were performed using Student’s t-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38438958", "locator": "sections[15] \"Statistical analysis\" paragraph 2", "quote": "Comparisons among more than two groups were performed using one-way analysis of variance (ANOVA) with Tukey’s post hoc test. Comparisons between two groups were performed using Student’s t-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38438958", "locator": "sections[29] \"Data availability\" paragraph 2", "quote": "The datasets used and/or analysed during the current study available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 318 HCC-specific SE-controlled genes were identified.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38438958", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 318 HCC-specific SE-controlled genes were identified."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "A total of 318 HCC-specific SE-controlled genes were identified.", "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:38438958"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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