ArticleCancer prevention research (Philadelphia, Pa.)2012
Deregulation of XPC and CypA by cyclosporin A: an immunosuppression-independent mechanism of skin carcinogenesis.
Article in Cancer prevention research (Philadelphia, Pa.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Sirolimus effects on cancer incidence after kidney transplantation: a meta-analysis.Cancer medicine · 2015Pooled it
- Merkel Cell Carcinoma and Immunosuppression, UV Radiation, and Merkel Cell Polyomavirus.JAMA dermatology · 2025Article
- Synergistic Effects of Sanglifehrin-Based Cyclophilin Inhibitor NV651 with Cisplatin in Hepatocellular Carcinoma.Cancers · 2022Article
- LINC01419-mediated epigenetic silencing of ZIC1 promotes metastasis in hepatocellular carcinoma through the PI3K/Akt signaling pathway.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- A Critical Role of Peptidylprolyl Isomerase A Pseudogene 22/microRNA-197-3p/Peptidylprolyl Isomerase A Axis in Hepatocellular Carcinoma.Frontiers in genetics · 2021Article
- Calcineurin inhibitor (CNI)-associated skin cancers: New insights on exploring mechanisms by which CNIs downregulate DNA repair machinery.Photodermatology, photoimmunology & photomedicine · 2020Review
- Cutaneous Squamous Cell Carcinoma: From Biology to Therapy.International journal of molecular sciences · 2020Review
- Astaxanthin enhances erlotinib-induced cytotoxicity by p38 MAPK mediated xeroderma pigmentosum complementation group C (XPC) down-regulation in human lung cancer cells.Toxicology research · 2018Article
- Optical-Spectrometry-Based Method for Immunosuppressant Medicine Level Detection in Aqueous Solutions.Sensors (Basel, Switzerland) · 2018Article
- Phosphorylation of xeroderma pigmentosum group C regulates ultraviolet-induced DNA damage repair.Nucleic acids research · 2018Article
- Cyclophilin J PPIase Inhibitors Derived from 2,3-Quinoxaline-6 Amine Exhibit Antitumor Activity.Frontiers in pharmacology · 2018Article
- Merkel cell carcinoma: Epidemiology, pathogenesis, diagnosis and therapy.Reviews in endocrine & metabolic disorders · 2017Review
- Risk of Second Malignancies in Solid Organ Transplant Recipients Who Develop Keratinocyte Cancers.Cancer research · 2017Article
- Cancer in Solid Organ Transplant Recipients: There Is Still Much to Learn and Do.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Article
- Spectrum of Immune-Related Conditions Associated with Risk of Keratinocyte Cancers among Elderly Adults in the United States.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2017Article
- Article
- Effect of a quality-controlled fermented nutraceutical on skin aging markers: An antioxidant-control, double-blind study.Experimental and therapeutic medicine · 2016Article
- Melanoma Risk and Survival among Organ Transplant Recipients.The Journal of investigative dermatology · 2015Article
- XPC inhibits NSCLC cell proliferation and migration by enhancing E-Cadherin expression.Oncotarget · 2015Article
- Risk of merkel cell carcinoma after solid organ transplantation.Journal of the National Cancer Institute · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Skin cancer is the most common malignancy in organ transplant recipients, causing serious morbidity and mortality. Preventing and treating skin cancer in these individuals has been extraordinarily challenging. Following organ transplantation, cyclosporin A (CsA) has been used as an effective immunosuppressive to prevent rejection. Therefore immunosuppression has been widely assumed to be the major cause for increased skin carcinogenesis. However, the mechanism of skin carcinogenesis in organ transplant recipients has not been understood to date; specifically, it remains unknown whether these cancers are immunosuppression dependent or independent. Here, using both immunocompromised nude mice which are defective in mature T lymphocytes as an in vivo model and human keratinocytes as an in vitro model, we showed that CsA impairs genomic integrity in the response of keratinocytes to ultra violet B (UVB). Following UVB radiation, CsA inhibited UVB-induced DNA damage repair by suppressing the transcription of the DNA repair factor xeroderma pigmentosum C (XPC). In addition, CsA compromised the UVB-induced checkpoint function by upregulating the molecular chaperone protein cyclophilin A (CypA). XPC mRNA levels were lower, whereas CypA mRNA and protein levels were higher in human skin cancers than in normal skin. CsA-induced phosphoinositide 3-kinase(PI3K)/AKT activation was required for both XPC suppression and CypA upregulation. Blocking UVB damage or inhibiting the PI3K/AKT pathway prevented CsA-sensitized skin tumorigenesis. Our findings identified deregulation of XPC and CypA as key targets of CsA, and UVB damage and PI3K/AKT activation as two principal drivers for CsA-sensitized skin tumorigenesis, further supporting an immunosuppression-independent mechanism of CsA action on skin tumorigenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.