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Published on: February 15, 2017
UVB drives different stages of epigenome alterations during progression of skin cancer
Yuqing Yang1, Renyi Wu2, Davit Sargsyan2
1Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Abstract:
Exposure to ultraviolet B (UVB) irradiation results in multitude of cellular responses including generation of reactive oxygen species and DNA damage and is responsible for non-melanoma skin cancers (NMSCs). Although genetic mutation is well documented, the epi-mutation, the alteration in epigenetics, remains elusive. In this study, we utilized CpG Methyl-seq to identify a genome-wide DNA CpG methylation, to profile the DNA methylation in UVB-irradiated SKH-1 mouse skin epidermis and non-melanoma skin papillomas at various stages. Methyl-seq and RNA-seq were performed to examine the methylation and corresponding transcriptome alterations. The methylation profiles in mouse epidermis were altered by UVB-irradiation as time progresses. Ingenuity Pathways Analysis (IPA) identified many cancer related pathways including PTEN, p53, Nrf2 and inflammatory signaling in UVB-irradiation induced carcinogenesis. Additionally, some novel genes involved in skin carcinogenesis that were not previously reported were differentially methylated, including Enf2, Mgst2, Vegfa, and Cdk4. Taken together, the current study provides novel profiles and insights of methylation and transcriptomic changes at different stages of carcinogenesis in UVB-irradiation induced NMSC and offers potential targets for prevention and treatment of NMSC at different stages of human skin cancer.
Insights
UVB irradiation alters DNA methylation in mouse skin, impacting cancer-related pathways and identifying novel genes. These findings offer potential targets for non-melanoma skin cancer prevention and treatment.
Area of Science:
- Oncology
- Epigenetics
- Dermatology
Background:
- Ultraviolet B (UVB) irradiation causes DNA damage and is linked to non-melanoma skin cancers (NMSCs).
- While genetic mutations are known drivers, epigenetic alterations (epi-mutations) in NMSC development remain less understood.
- Understanding epigenetic changes is crucial for comprehensive NMSC research.
Purpose of the Study:
- To investigate genome-wide DNA CpG methylation profiles in UVB-irradiated mouse skin at various stages of carcinogenesis.
- To correlate DNA methylation changes with transcriptome alterations in UVB-induced NMSC.
- To identify novel genes and pathways involved in skin cancer development.
Main Methods:
- Utilized CpG Methyl-seq for genome-wide DNA methylation profiling.
- Performed RNA-seq to analyze corresponding transcriptome alterations.
- Employed Ingenuity Pathway Analysis (IPA) to identify cancer-related signaling pathways.
Main Results:
- UVB irradiation progressively altered DNA methylation profiles in mouse epidermis over time.
- IPA revealed significant alterations in cancer-related pathways, including PTEN, p53, Nrf2, and inflammatory signaling.
- Identified novel differentially methylated genes (Enf2, Mgst2, Vegfa, Cdk4) implicated in skin carcinogenesis.
Conclusions:
- UVB-induced NMSC involves dynamic changes in DNA methylation and gene expression.
- The study provides novel insights into the epigenetic landscape of skin carcinogenesis.
- Identified potential therapeutic and preventative targets for NMSC at different disease stages.
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