Transcriptome Analysis Identifies the Dysregulation of Ultraviolet Target Genes in Human Skin Cancers

Area of Science:

• Molecular biology
• Dermatology
• Cancer research

Background:

• Ultraviolet radiation (UVR) is a primary risk factor for skin cancers.
• UVR induces mutagenic effects and transcriptional instability in skin cells.
• Transcriptional instability may play a key role in skin cancer development.

Purpose of the Study:

• To characterize kinetic changes in global gene expression in human keratinocytes after UVR exposure.
• To identify UV-responsive genes (UVSGs) with conserved and persistent changes in mRNA levels.
• To investigate the role of UVSGs in skin cancer proliferation, survival, and clinical diagnosis.

Main Methods:

• Transcriptomic profiling of human keratinocytes exposed to UVR.
• Identification of UV signature genes (UVSGs) based on conserved UV-responsiveness and persistent mRNA changes.
• Computational Gene Set Enrichment Analysis to assess UVSG dysregulation in human skin cancers.

Main Results:

• A subset of UV-responsive genes (UVSGs) exhibited conserved and persistent changes in mRNA levels post-UVR exposure.
• Eleven UVSGs were identified as critical for skin cancer cell proliferation and survival.
• A significant portion of UVSGs were found to be dysregulated in human squamous cell carcinomas, but not other cancers.

Conclusions:

• UVSGs are specifically linked to UVR-induced transcriptional instability and skin carcinogenesis.
• UVSGs hold potential for clinical diagnosis of UV damage.
• UVSGs may be valuable biomarkers for stratifying skin cancer risk.