NEDD8 promotes radioresistance via triggering autophagy formation and serves as a novel prognostic marker in oral squamous cell carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36890567", "kind": "science-record", "revision": 3, "content_hash": "sha256:c5745ae9a25748014e6d5b71cbb351fb36ada33ebd7ececd040362164d70f0f2", "created_at": "2026-11-01T19:01:31Z", "updated_at": "2026-11-01T22:09:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "NEDD8 promotes radioresistance via triggering autophagy formation and serves as a novel prognostic marker in oral squamous cell carcinoma.", "doi": "10.1186/s12935-023-02883-0", "pmid": "36890567", "authors": ["Tsu-Zong Yuan", "Hui-Yu Lin", "Chia-Hao Kuei", "Che-Hsuan Lin", "Hsun-Hua Lee", "Hsin-Lun Lee", "Hsiao-Wei Lu", "Chia-Yi Su", "Hui-Wen Chiu", "Yuan-Feng Lin"], "journal": "Cancer cell international", "year": 2023, "abstract": "BACKGROUND: Radiotherapy is the first-line regimen for treating oral squamous cell carcinoma (OSCC) in current clinics. However, the development of therapeutic resistance impacts the anticancer efficacy of irradiation in a subpopulation of OSCC patients. As a result, discovering a valuable biomarker to predict radiotherapeutic effectiveness and uncovering the molecular mechanism for radioresistance are clinical issues in OSCC.\nMETHODS: Three OSCC cohorts from The Cancer Genome Atlas (TCGA), GSE42743 dataset and Taipei Medical University Biobank were enrolled to examine the transcriptional levels and prognostic significance of neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8). Gene set enrichment analysis (GSEA) was utilized to predict the critical pathways underlying radioresistance in OSCC. The colony-forming assay was used to estimate the consequences of irradiation sensitivity after the inhibition or activation of the NEDD8-autophagy axis in OSCC cells.\nRESULTS: NEDD8 upregulation was extensively found in primary tumors compared to normal adjacent tissues and potentially served as a predictive marker for the therapeutic effectiveness of irradiation in OSCC patients. NEDD8 knockdown enhanced radiosensitivity but NEDD8 overexpression reduced it in OSCC cell lines. The inclusion of MLN4924, a pharmaceutical inhibitor for NEDD8-activating enzyme, dose-dependently restored the cellular sensitivity to irradiation treatment in irradiation-insensitive OSCC cells. Computational simulation by GSEA software and cell-based analyses revealed that NEDD8 upregulation suppresses Akt/mTOR activity to initiate autophagy formation and ultimately confers radioresistance to OSCC cells.\nCONCLUSION: These findings not only identify NEDD8 as a valuable biomarker to predict the efficacy of irradiation but also offer a novel strategy to overcome radioresistance via targeting NEDD8-mediated protein neddylation in OSCC.", "claims": [{"id": "claim-method", "statement": "A paired t test was utilized to compare NEDD8 gene expression in cancer tissues and corresponding normal tissues.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36890567", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "A paired t test was utilized to compare NEDD8 gene expression in cancer tissues and corresponding normal tissues."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Not applicable.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36890567", "locator": "sections[23] \"ack\" paragraph 1", "quote": "Not applicable."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We found that the mRNA levels of NEDD8 in primary tumors were significantly (p = 0.022) higher than those in normal tissues from TCGA oral cancer patients but not nonoral cancer patients (Fig. 1A).", "kind": "quantitative", "target": {"value": 0.022, "unit": "p-value", "tolerance": null, "source": "We found that the mRNA levels of NEDD8 in primary tumors were significantly (p = 0.022) higher than those in normal tissues from TCGA oral cancer patients but not nonoral cancer patients (Fig. 1A)."}, "evidence": [{"asset": "source:pmid:36890567", "locator": "sections[13] \"NEDD8 upregulation is extensively detected in primary tumors compared to normal tissues and is related to a poorer prognosis in oral cancer\" paragraph 2", "quote": "We found that the mRNA levels of NEDD8 in primary tumors were significantly (p = 0.022) higher than those in normal tissues from TCGA oral cancer patients but not nonoral cancer patients (Fig. 1A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We found that the mRNA levels of NEDD8 in primary tumors were significantly (p = 0.022) higher than those in normal tissues from TCGA oral cancer patients but not nonoral cancer patients (Fig. 1A).", "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:36890567"], "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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