Knock-down of the TIM/TIPIN complex promotes apoptosis in melanoma cells.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32499870", "kind": "science-record", "revision": 8, "content_hash": "sha256:1d2c5658bc1717ce9f13a71c6aaeceeabadaf968c931b78512693f6a3f8a6b29", "created_at": "2026-11-01T15:41:03Z", "updated_at": "2026-11-01T22:44:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Knock-down of the TIM/TIPIN complex promotes apoptosis in melanoma cells.", "doi": "10.18632/oncotarget.27572", "pmid": "32499870", "authors": ["Abhijit Chakraborty", "Faisal Aziz", "Eunmiri Roh", "Le Thi My Le", "Raja Dey", "Tianshun Zhang", "Moeez G Rathore", "Aalekhya Sharma Biswas", "Ann M Bode", "Zigang Dong"], "journal": "Oncotarget", "year": 2020, "abstract": "The Timeless (TIM) and it's interacting partner TIPIN protein complex is well known for its role in replication checkpoints and normal DNA replication processes. Recent studies revealed the involvement of TIM and TIPIN in human malignancies; however, no evidence is available regarding the expression of the TIM/TIPIN protein complex or its potential role in melanoma. Therefore, we investigated the role of this complex in melanoma. To assess the role of the TIM/TIPIN complex in melanoma, we analyzed TIM/TIPIN expression data from the publicly accessible TCGA online database, Western blot analysis, and RT-qPCR in a panel of melanoma cell lines. Lentivirus-mediated TIM/TIPIN knockdown in A375 melanoma cells was used to examine proliferation, colony formation, and apoptosis. A xenograft tumor formation assay was also performed. The TIM/TIPIN complex is frequently overexpressed in melanoma cells compared to normal melanocytes. We also discovered that the overexpression of TIM and TIPIN was significantly associated with poorer prognosis of melanoma patients. Furthermore, we observed that shRNA-mediated knockdown of TIM and TIPIN reduced cell viability and proliferation due to the induction of apoptosis and increased levels of γH2AX, a marker of DNA damage. In a xenograft tumor nude mouse model, shRNA-knockdown of TIM/TIPIN significantly reduced tumor growth. Our results suggest that the TIM/TIPIN complex plays an important role in tumorigenesis of melanoma, which might reveal novel approaches for the development of new melanoma therapies. Our studies also provide a beginning structural basis for understanding the assembly of the TIM/TIPIN complex. Further mechanistic investigations are needed to determine the complex's potential as a biomarker of melanoma susceptibility. Targeting TIM/TIPIN might be a potential therapeutic strategy against melanoma.", "claims": [{"id": "claim-method", "statement": "Analysis of variance was used to calculate differential expression.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32499870", "locator": "sections[3] \"TIM and TIPIN are overexpressed in melanoma cells\" paragraph 2", "quote": "Analysis of variance was used to calculate differential expression."}], "state": "complete"}, {"id": "claim-data-access", "statement": "To investigate the role of TIM and TIPIN in the progression of melanoma, we first analyzed TIM and TIPIN expression in 461 melanoma tissue samples and 558 normal tissue samples from The Cancer Genome Atlas (TCGA) Data Portal.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32499870", "locator": "sections[3] \"TIM and TIPIN are overexpressed in melanoma cells\" paragraph 2", "quote": "To investigate the role of TIM and TIPIN in the progression of melanoma, we first analyzed TIM and TIPIN expression in 461 melanoma tissue samples and 558 normal tissue samples from The Cancer Genome Atlas (TCGA) Data Portal."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:32499870"], "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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