Cytosine-phosphate-guanine oligodeoxynucleotides alleviate radiation-induced kidney injury in cervical cancer by inhibiting DNA damage and oxidative stress through blockade of PARP1/XRCC1 axis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37773127", "kind": "science-record", "revision": 4, "content_hash": "sha256:a686b6ee04768ebd05bc25ee6f20ca33a1f986c2ca967274e7ee98fde3a01a6d", "created_at": "2026-11-01T19:02:37Z", "updated_at": "2026-11-01T22:52:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Cytosine-phosphate-guanine oligodeoxynucleotides alleviate radiation-induced kidney injury in cervical cancer by inhibiting DNA damage and oxidative stress through blockade of PARP1/XRCC1 axis.", "doi": "10.1186/s12967-023-04548-y", "pmid": "37773127", "authors": ["Deyu Zhang", "Shitai Zhang", "Zheng He", "Ying Chen"], "journal": "Journal of translational medicine", "year": 2023, "abstract": "BACKGROUND: Radiotherapy can cause kidney injury in patients with cervical cancer. This study aims to investigate the possible molecular mechanisms by which CpG-ODNs (Cytosine phosphate guanine-oligodeoxynucleotides) regulate the PARP1 (poly (ADP-ribose) polymerase 1)/XRCC1 (X-ray repair cross-complementing 1) signaling axis and its impact on radiation kidney injury (RKI) in cervical cancer radiotherapy.\nMETHODS: The GSE90627 dataset related to cervical cancer RKI was obtained from the Gene Expression Omnibus (GEO) database. Bioinformatics databases and R software packages were used to analyze the target genes regulated by CpG-ODNs. A mouse model of RKI was established by subjecting C57BL/6JNifdc mice to X-ray irradiation. Serum blood urea nitrogen (BUN) and creatinine levels were measured using an automated biochemical analyzer. Renal tissue morphology was observed through HE staining, while TUNEL staining was performed to detect apoptosis in renal tubular cells. ELISA was conducted to measure levels of oxidative stress-related factors in mouse serum and cell supernatant. An in vitro cell model of RKI was established using X-ray irradiation on HK-2 cells for mechanism validation. RT-qPCR was performed to determine the relative expression of PARP1 mRNA. Cell proliferation activity was assessed using the CCK-8 assay, and Caspase 3 activity was measured in HK-2 cells. Immunofluorescence was used to determine γH2AX expression.\nRESULTS: Bioinformatics analysis revealed that the downstream targets regulated by CpG-ODNs in cervical cancer RKI were primarily PARP1 and XRCC1. CpG-ODNs may alleviate RKI by inhibiting DNA damage and oxidative stress levels. This resulted in significantly decreased levels of BUN and creatinine in RKI mice, as well as reduced renal tubular and glomerular damage, lower apoptosis rate, decreased DNA damage index (8-OHdG), and increased levels of antioxidant factors associated with oxidative stress (SOD, CAT, GSH, GPx). Among the CpG-ODNs, CpG-ODN2006 had a more pronounced effect. CpG-ODNs mediated the inhibition of PARP1, thereby suppressing DNA damage and oxidative stress response in vitro in HK-2 cells. Additionally, PARP1 promoted the formation of the PARP1 and XRCC1 complex by recruiting XRCC1, which in turn facilitated DNA damage and oxidative stress response in renal tubular cells. Overexpression of either PARP1 or XRCC1 reversed the inhibitory effects of CpG-ODN2006 on DNA damage and oxidative stress in the HK-2 cell model and RKI mouse model.\nCONCLUSION: CpG-ODNs may mitigate cervical cancer RKI by blocking the activation of the PARP1/XRCC1 signaling axis, inhibiting DNA damage and oxidative stress response in renal tubule epithelial cells.", "claims": [{"id": "claim-method", "statement": "Independent sample t-test was used for comparison between two groups, and data between multiple groups were compared by one-way ANOVA, followed by Tukey post hoc test. Absorbance values at multiple time points were compared using two-way ANOVA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37773127", "locator": "sections[21] \"Statistical analysis\" paragraph 2", "quote": "Independent sample t-test was used for comparison between two groups, and data between multiple groups were compared by one-way ANOVA, followed by Tukey post hoc test. Absorbance values at multiple time points were compared using two-way ANOVA."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analysed during the current study are available in the manuscript and Additional files 1–3.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37773127", "locator": "sections[38] \"notes\" paragraph 1", "quote": "The datasets generated and/or analysed during the current study are available in the manuscript and Additional files 1–3."}], "state": "complete"}, {"id": "claim-target-result", "statement": "CpG-ODNs may mitigate cervical cancer RKI by blocking the activation of the PARP1/XRCC1 signaling axis, inhibiting DNA damage and oxidative stress response in renal tubule epithelial cells.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37773127", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "CpG-ODNs may mitigate cervical cancer RKI by blocking the activation of the PARP1/XRCC1 signaling axis, inhibiting DNA damage and oxidative stress response in renal tubule epithelial cells."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "CpG-ODNs may mitigate cervical cancer RKI by blocking the activation of the PARP1/XRCC1 signaling axis, inhibiting DNA damage and oxidative stress response in renal tubule epithelial cells.", "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:37773127"], "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:GSE90627"], "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": {}, "inputs": ["data:geo:GSE90627"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37773127", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12967-023-04548-y", "sha256": 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A mouse model of RKI was established by subjecting C57BL/6", "dative stress in the HK-2 cell model and RKI mouse model. CONCLUSION: CpG-ODNs may mitigate cervical", "ze the target genes regulated by CpG-ODNs. A mouse model of RKI was established by subjecting C", "evels of oxidative stress-related factors in mouse serum and cell supernatant. An in vitro cell"], "order_basis": "paper_text_order:792", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["while TUNEL staining was performed to detect apoptosis in renal tubular cells. ELISA was conducted", "d renal tubular and glomerular damage, lower apoptosis rate, decreased DNA damage index (8-OHdG), a", "roliferation activity was assessed using the CCK-8 assay, and Caspase 3 activity was measured i", "vity was assessed using the CCK-8 assay, and Caspase 3 activity was measured in HK-2 cells. Immun"], "order_basis": "paper_text_order:1094", "id": "assay:2"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["to detect apoptosis in renal tubular cells. 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