Similar Datasets
Project description: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.
| S-EPMC6411449 | biostudies-literature
Project description:Exposure to UVB irradiation results in multitude of cellular responses including generation of reactive oxygen species (ROS) 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. DNA methylation is a stable and heritable epigenetic change in the control of gene expression. Furthermore, it is unclear how the epigenomic DNA methylome would change during progression of UVB-induced carcinogenesis. In this study, we utilized CpG Methyl-seq to identify a genome-wide DNA CpG methylation, to profile the DNA methylation in ultraviolet B (UVB)-irradiated SKH-1 mouse skin epidermis and non-melanoma skin papillomas at various stages. Agilent mouse SureSelect Methyl-seq Kit was used for enrichment of about 3.3 million CpG sites in the mouse genome. Simultaneously, RNA-seq was performed to examine the corresponding transcriptome alterations. Bioinformatic analysis was utilized to identify differentially methylated and differentially expressed genes. The methylation profiles in mouse epidermis were altered by UVB-irradiation as time progresses. Comparing all epidermis samples at week-15 versus week-25, UVB had great impact on DNA methylome alteration. Examination of the differentially methylated regions (DMRs), most of the DMRs were located in the distal intragenic (>3 kb upstream of TSS or downstream of 3’ UTR) and the promoter regions. Interestingly, at week-25 the methylation profiles between the whole skin versus the tumor samples were different. Ingenuity Pathways Analysis (IPA) identified many cancer related pathways including PTEN, p53, Nrf2 and inflammatory signaling in UVB-irradiation induced carcinogenesis. Cell cycle regulation and cell growth related pathways including State3 signaling and estrogen-mediated S-phase entry were also identified. Additionally, some novel genes involved in skin carcinogenesis that were not previously reported were differentially methylated, including Enf2, Mgst2, Vegfa, and Cdk4. The methylation and expression of these genes were validated by pyrosequencing and qPCR. Taken together, the current study provides novel profiles of methylation and transcriptomic changes at different stages of carcinogenesis in UVB-irradiation induced NMSC and offer potential targets for prevention and treatment of NMSC at different stages of human skin cancer.
2019-03-20 | GSE122226 | GEO
Project description:Exposure to UVB irradiation results in multitude of cellular responses including generation of reactive oxygen species (ROS) 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. DNA methylation is a stable and heritable epigenetic change in the control of gene expression. Furthermore, it is unclear how the epigenomic DNA methylome would change during progression of UVB-induced carcinogenesis. In this study, we utilized CpG Methyl-seq to identify a genome-wide DNA CpG methylation, to profile the DNA methylation in ultraviolet B (UVB)-irradiated SKH-1 mouse skin epidermis and non-melanoma skin papillomas at various stages. Agilent mouse SureSelect Methyl-seq Kit was used for enrichment of about 3.3 million CpG sites in the mouse genome. Simultaneously, RNA-seq was performed to examine the corresponding transcriptome alterations. Bioinformatic analysis was utilized to identify differentially methylated and differentially expressed genes. The methylation profiles in mouse epidermis were altered by UVB-irradiation as time progresses. Comparing all epidermis samples at week-15 versus week-25, UVB had great impact on DNA methylome alteration. Examination of the differentially methylated regions (DMRs), most of the DMRs were located in the distal intragenic (>3 kb upstream of TSS or downstream of 3’ UTR) and the promoter regions. Interestingly, at week-25 the methylation profiles between the whole skin versus the tumor samples were different. Ingenuity Pathways Analysis (IPA) identified many cancer related pathways including PTEN, p53, Nrf2 and inflammatory signaling in UVB-irradiation induced carcinogenesis. Cell cycle regulation and cell growth related pathways including State3 signaling and estrogen-mediated S-phase entry were also identified. Additionally, some novel genes involved in skin carcinogenesis that were not previously reported were differentially methylated, including Enf2, Mgst2, Vegfa, and Cdk4. The methylation and expression of these genes were validated by pyrosequencing and qPCR. Taken together, the current study provides novel profiles of methylation and transcriptomic changes at different stages of carcinogenesis in UVB-irradiation induced NMSC and offer potential targets for prevention and treatment of NMSC at different stages of human skin cancer.
2019-03-20 | GSE122225 | GEO
Project description:UVB drives different stages of epigenome alterations during progression of skin cancer
| PRJNA504022 | ENA
Project description:UVB drives different stages of epigenome alterations during progression of skin cancer [Bisulfite-seq]
| PRJNA504025 | ENA
Project description:UVB drives different stages of epigenome alterations during progression of skin cancer [RNA-Seq]
| PRJNA504024 | ENA
Project description:Nonmelanoma skin cancers (NMSCs) are the most common type of skin cancers. Major risk factors for NMSCs include exposure to ultraviolet (UV) irradiation. Ursolic acid (UA) is a natural triterpenoid enriched in blueberries and herbal medicinal products, and possess anticancer activities. This study focuses on the impact of UA on epigenomic, genomic mechanisms and prevention of UVB-mediated NMSC. CpG methylome and RNA transcriptome alterations of early, promotion and late stages of UA treated on UVB-induced NMSC in SKH-1 hairless mice were conducted using CpG methyl-seq and RNA-seq. Samples were collected at weeks 2, 15, and 25, and integrated bioinformatic analyses were performed to identify key pathways and genes modified by UA against UVB-induced NMSC. Morphologically, UA significantly reduced NMSC tumor volume and tumor number. DNA methylome showed inflammatory pathways IL-8, NF-κB, and Nrf2 pathways were highly involved. Antioxidative stress master regulator Nrf2, cyclin D1, DNA damage, and anti-inflammatory pathways were induced by UA. Nrf2, cyclin D1, TNFrsf1b, and Mybl1 at early (2 weeks) and late (25 weeks) stages were identified and validated by quantitative polymerase chain reaction. In summary, integration of CpG methylome and RNA transcriptome studies show UA alters antioxidative, anti-inflammatory, and anticancer pathways in UVB-induced NMSC carcinogenesis. Particularly, UA appears to drive Nrf2 and its upstream/downstream genes, anti-inflammatory (at early stages) and cell cycle regulatory (both early and late stages) genes, of which might contribute to the overall chemopreventive effects of UVB-induced MNSC. This study may provide potential biomarkers/targets for chemoprevention of early stage of UVB-induced NMSC in human.
| S-EPMC6722003 | biostudies-literature
Project description:While obesity represents one of several risk factors for colorectal cancer in humans, the mechanistic underpinnings of this association remain unresolved. Environmental stimuli, including diet, can alter the epigenetic landscape of DNA cis-regulatory elements affecting gene expression and phenotype. Here, we explored the impact of diet and obesity on gene expression and the enhancer landscape in murine colonic epithelium. Obesity led to the accumulation of histone modifications associated with active enhancers at genomic loci downstream of signaling pathways integral to the initiation and progression of colon cancer. Meanwhile, colon-specific enhancers lost the same histone mark, poising cells for loss of differentiation. These alterations reflect a transcriptional program with many features shared with the program driving colon cancer progression. The interrogation of enhancer alterations by diet in colonic epithelium provides insights into the biology underlying high-fat diet and obesity as risk factors for colon cancer.
| S-EPMC4050048 | biostudies-literature
Project description:Phosphatase and tensin homolog located on chromosome 10 (PTEN) is a tumor suppressor gene and one of the most frequently mutated/deleted genes in human prostate cancer (PCa). However, how PTEN deletion would impact the epigenome and transcriptome alterations remain unknown. This hypothesis was tested in a prostate-specific PTEN-/- (KO) mouse prostatic adenocarcinoma model through DNA methyl-Seq and RNA-Seq analyses. Examination of cancer genomic datasets revealed that PTEN is expressed at lower levels in PTEN-deleted tumor samples than in normal solid tissue samples. Methylome and transcriptome profiling identified several inflammatory responses and immune response signaling pathways, including NF-kB signaling, IL-6 signaling, LPS/IL-1-mediated inhibition of RXR Function, PI3K in B lymphocytes, iCOS-iCOSL in T helper cells, and the role of NFAT in regulating the immune response, were affected by PTEN deletion. Importantly, a small subset of genes that showed DNA hypermethylation or hypomethylation was correlated with decreased or increased gene expression including CXCL1. quantitative polymerase chain reaction analyses of representative genes validated the RNA-Seq results. Histopathological examinations showed that the severity of prostatic intraepithelial neoplasia and inflammation development gradually increased as PTEN null mice aged. Collectively, these findings suggest that loss of PTEN drives global changes in DNA CpG methylation and transcriptomic gene expression and highly associated with several inflammatory and immune molecular pathways during PCa development. These biomarkers could be valuable molecular targets for cancer drug discovery and development against PCa.
| S-EPMC6956734 | biostudies-literature
Project description:The focus of this research was on UVB radiation (280-320 nm) responsible for cellular changes in skin of acute and chronically exposed individuals. This study investigated the acute cellular damages triggered by UVB exposure of cultured human fibroblasts and keratinocyte cells immediately and 24 h post exposure in order to understand damage onset and progression. The study evaluated a number of cellular parameters including mitochondria, lysosomes, cell membrane, DNA damages as well as pro and anti-apoptotic protein expression levels. Cellular organelle damages were assessed by a battery of in vitro toxicological assays using MTS and Neutral red cytotoxicity assays. Cell membrane damages were also assessed by measuring lactate dehydrogenase (LDH) enzyme leakage from UVB exposed cells. Lastly DNA damages was assessed using the comet assay while protein expression was evaluated using Western Blot. In this study we reported in all our assay systems (MTS, NR and LDH) that cellular damages were UVB dose dependent with damages amplified 24 h post exposure. Our results also indicated that incubation of exposed cells for a period of 24 h increased the sensitivity of the assay systems used. The increased sensitivity in detecting early cytotoxic damages was manifested though organelle damage measurement at very low doses which were not manifested immediately post exposure. The data also indicated that HaCaT cells were most sensitive in detecting UVB triggered damages immediately and 24 h post exposure using the MTS assay. We also established upregulation and downregulation of various apoptotic proteins at various time points post exposure. The presented data clearly indicated the need for a comprehensive assessment of UVB damages 4 and 24 h post exposure due to the different assay sensitivities in addition to various signaling mechanisms activated at different time points post exposure.
| S-EPMC5615164 | biostudies-literature