title: Transcriptome Analysis Identifies the Dysregulation of Ultraviolet Target Genes in Human Skin Cancers.
abstract: 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.
authors.affiliation: Department of Systems Biology, Columbia University, New York, NY, United States of America.
authors.forename: Yao
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Dermatology, Columbia University, New York, NY, United States of America.
authors.forename: Arianna L
authors.initials: AL
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Columbia University, New York, NY, United States of America.
authors.forename: Rong
authors.initials: R
authors.lastname: Du
authors.affiliation: Department of Dermatology, Columbia University, New York, NY, United States of America.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D004307:Dose-Response Relationship, Radiation; D020869:Gene Expression Profiling; D006801:Humans; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome; D014466:Ultraviolet Rays