UVB drives different stages of epigenome alterations during progression of skin cancer

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 genomewide 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

DNA methylome and transcriptome alterations and cancer prevention by triterpenoid ursolic acid in UVB‐induced skin tumor in mice

“…Acetone (HPLC grade) and 10% phosphate‐buffered formalin were obtained from Fisher Scientific (Hampton, NH). UV lamps that emit UV0042 (280‐320 nm; 75%‐80% of total energy) and UVA (320‐375 nm; 20%‐25% of total energy) were used as described in previous studies . The dose of UVB was quantified using a UVB Spectra 305 dosimeter (Daavlin Co., Bryan, OH‐).…”

“…Female SKH‐1 hairless mice were purchased from Charles River Laboratories (Wilmington, MA) at 5 weeks of age, as described in previous studies . These mice were maintained at a controlled temperature (20‐22°C) and humidity (45%‐55%) under 12‐hour light and dark cycles at the Rutgers Animal Facility.…”

Long non-coding RNAs in cutaneous biology and keratinocyte carcinomas

“…Conversely, BCC is strongly associated with aberrant activation of the Hedgehog signaling pathway due to loss of PTCH1 receptor function and activation of the G protein-coupled receptor SMO [17][18][19]. Like many other cancers, cSCCs and BCCs are associated with epigenetic deregulation and aberrant DNA methylation, which also contribute to cancer progression [30][31][32][33][34].…”

Cytogenomics of murine melanoma cell lines C57/B1 and B16-F0

“…It is a truism that during initiation, promotion and progression of skin cancer, changes in DNA and chromosomes are involved. 6 Thus, genetic studies are necessary to better understand melanoma biology, which also need to be combined with tests of novel melanoma therapeutics. 5 Genes recently brought to the focus of melanoma research were those involved in pigmentation, DNA repair, immune response, metabolism and/or are vitamin D receptor polymorphisms.…”