POLE2 promotes osteosarcoma progression by enhancing the stability of CD44.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38627379", "kind": "science-record", "revision": 4, "content_hash": "sha256:af2c29775b21716e9517f308ba1fcd92938555e868142637d43860a7869f6c4d", "created_at": "2026-11-01T19:20:36Z", "updated_at": "2026-11-01T22:54:09Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "POLE2 promotes osteosarcoma progression by enhancing the stability of CD44.", "doi": "10.1038/s41420-024-01875-x", "pmid": "38627379", "authors": ["Baichuan Wang", "Hongzhi Hu", "Xiaohui Wang", "Zengwu Shao", "Deyao Shi", "Fashuai Wu", "Jianxiang Liu", "Zhicai Zhang", "Juan Li", "Zhidao Xia", "Weijian Liu", "Qiang Wu"], "journal": "Cell death discovery", "year": 2024, "abstract": "Osteosarcoma (OS) is the most prevalent primary malignancy of bone in children and adolescents. It is extremely urgent to develop a new therapy for OS. In this study, the GSE14359 chip from the GEO database was used to screen differentially expressed genes in OS. DNA polymerase epsilon 2 (POLE2) was confirmed to overexpress in OS tissues and cell lines by immunohistochemical staining, qPCR and Western blot. Knockdown of POLE2 inhibited the proliferation and migration of OS cells in vitro, as well as the growth of tumors in vivo, while the apoptosis rate was increased. Bioinformatics analysis revealed that CD44 and Rac signaling pathway were the downstream molecule and pathway of POLE2, which were inhibited by knockdown of POLE2. POLE2 reduced the ubiquitination degradation of CD44 by acting on MDM2. Moreover, knockdown of CD44 inhibited the tumor-promoting effects of POLE2 overexpression on OS cells. In conclusion, POLE2 augmented the expression of CD44 via inhibiting MDM2-mediated ubiquitination, and then activated Rac signaling pathway to influence the progression of OS, indicating that POLE2/CD44 might be potential targets for OS treatment.", "claims": [{"id": "claim-method", "statement": "The data was then analyzed by Limma package of R studio and the screening criteria for differentially expressed genes were |log2 fold change| > 1 with the adjusted P value < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38627379", "locator": "sections[9] \"Microarrays analysis from GEO database\" paragraph 2", "quote": "The data was then analyzed by Limma package of R studio and the screening criteria for differentially expressed genes were |log2 fold change| > 1 with the adjusted P value < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data used in this article is showed in the article and supplementary materials.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38627379", "locator": "sections[32] \"Data availability\" paragraph 2", "quote": "All data used in this article is showed in the article and supplementary materials."}], "state": "complete"}, {"id": "claim-target-result", "statement": "DNA polymerase epsilon 2 (POLE2) was confirmed to overexpress in OS tissues and cell lines by immunohistochemical staining, qPCR and Western blot.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38627379", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "DNA polymerase epsilon 2 (POLE2) was confirmed to overexpress in OS tissues and cell lines by immunohistochemical staining, qPCR and Western blot."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "DNA polymerase epsilon 2 (POLE2) was confirmed to overexpress in OS tissues and cell lines by immunohistochemical staining, qPCR and Western blot.", "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:38627379"], "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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Knockdown o", "um test was used to analyze the quantitative immunohistochemical results of POLE2 in OS tissues and normal ti"], "order_basis": "paper_text_order:390", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["cell lines by immunohistochemical staining, qPCR and Western blot. Knockdown of POLE2 inhibit"], "order_basis": "paper_text_order:420", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["es by immunohistochemical staining, qPCR and Western blot. Knockdown of POLE2 inhibited the proliferat"], "order_basis": "paper_text_order:428", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["stochemical staining, qPCR and Western blot. Knockdown of POLE2 inhibited the proliferation and mig", "nd pathway of POLE2, which were inhibited by knockdown of POLE2. POLE2 reduced the ubiquitination d", "adation of CD44 by acting on MDM2. Moreover, knockdown of CD44 inhibited the tumor-promoting effect", "), and hFOB1.19 cell line (human osteoblasts transfected with SV40) were purchased from BeNa Culture"], "order_basis": "paper_text_order:442", "id": "assay:4"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ls in vitro, as well as the growth of tumors in vivo, while the apoptosis rate was increased. Bio"], "order_basis": "paper_text_order:557", "id": "assay:5"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["l as the growth of tumors in vivo, while the apoptosis rate was increased. Bioinformatics analysis"], "order_basis": "paper_text_order:576", "id": "assay:6"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ection (Beijing, China). MNNG HOS cells were cultured in MEM with 10% fetal bovine serum (FBS). MG-63", "e serum (FBS). MG-63 and hFOB1.19 cells were cultured in DMEM-H with 10% FBS. U-2OS cells were cultur", "red in DMEM-H with 10% FBS. U-2OS cells were cultured in the RPMI-1640 with 10% FBS. SAOS-2 cells wer", "he RPMI-1640 with 10% FBS. SAOS-2 cells were cultured in the McCOY’s 5 A with 15% FBS. 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