Transcriptome Analysis Identifies the Dysregulation of Ultraviolet Target Genes in Human Skin Cancers
Open accessAbstract
Exposure to ultraviolet radiation (UVR) is a major risk factor for both melanoma and non-melanoma skin cancers. In addition to its mutagenic effect, UVR can also induce substantial transcriptional instability in skin cells affecting thousands of genes, including many cancer genes, suggesting that transcriptional instability may be another important etiological factor in skin photocarcinogenesis. In this study, we performed detailed transcriptomic profiling studies to characterize the kinetic changes in global gene expression in human keratinocytes exposed to different UVR conditions. We identified a subset of UV-responsive genes as UV signature genes (UVSGs) based on 1) conserved UV-responsiveness of this subset of genes among different keratinocyte lines; and 2) UV-induced persistent changes in their mRNA levels long after exposure. Interestingly, 11 of the UVSGs were shown to be critical to skin cancer cell proliferation and survival. Through computational Gene Set Enrichment Analysis, we demonstrated that a significant portion of the UVSGs were dysregulated in human skin squamous cell carcinomas, but not in other human malignancies. This highlights the potential and specificity of the UVSGs in clinical diagnosis of UV damage and stratification of skin cancer risk.
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Ultraviolet radiation causes significant changes in the skin and modifies immunological responses.
“Ultraviolet radiation has been shown to cause significant changes in the skin as well as modify immunological responses (Shen et al. 2016).”
From Skin protection from solar ultraviolet radiation using natural compounds: a review (2024) · cites this paper as Shen et al. 2016
The Results section (“Transcriptomic responses to different UVR conditions”; page unavailable) reports substantial UV-induced gene-expression changes in cultured human keratinocytes, including enrichment of inflammatory-response and leukocyte-activation pathways. This supports changes in skin cells and immune-related gene expression, but the Discussion cautions that cultured cells do not capture interactions among cell types in vivo; the paper does not directly establish a modified immunological response in skin. (LLM, conf=0.84)
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Skin protection from solar ultraviolet radiation using natural compounds: a review
Verma, A., Zanoletti, A., Kareem, K. Y., Adelodun, B., Kumar, P., Ajibade, F. O., Silva, L. F. O., Phillips, A. J., Kartheeswaran, T., Bontempi, E., et al. (2024) · Environmental Chemistry Letters · doi:10.1007/s10311-023-01649-4 · Cited by 102 · see citing works
- Authors
- Shen, Y., Kim, A. L., Du, R., & Liu, L.
- Affiliations
- Columbia University (US)
- Corresponding author
- Liu, Liang
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-09-19
- Volume
- 11
- Issue
- 9
- Pages
- e0163054
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5028058
- OpenAlex
- W2521246436
- Cited by
- 24
- References
- 5
- Citations by year
- 2024: 2 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 2
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Columbia Academic Commons (Columbia University)
- Funders
- Office of Extramural Research, National Institutes of Health (K01AR064315, P30 ES009089)
- American Skin Association
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR44535)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- ultraviolet radiation, skin cancer, keratinocytes, squamous cell carcinoma, melanoma, photocarcinogenesis, gene expression profiling
- MeSH terms
- Carcinoma, Squamous Cell, Dose-Response Relationship, Radiation, Humans, Skin Neoplasms, Ultraviolet Rays, Gene Expression Profiling, Cell Proliferation, Transcriptome
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