DNA methylation/hydroxymethylation in melanoma

Fu, Siqi; Wu, Haijing; Zhang, Huiming; Lian, Christine G.; Lu, Qianjin

doi:10.18632/oncotarget.18293

Cited by 43 publications

(38 citation statements)

References 113 publications

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“…There have been studies suggesting the involvement of DNA methylation with the melanocyte lineage or pigmentation disorders, and most of them examined changes in melanoma . In this study, we revealed the significance of DNA methylation in the pigmentation in SLs, which we believe is a great step for further understanding of how UV radiation affects our skin.…”

Section: Discussionmentioning

confidence: 56%

UV irradiation‐induced DNA hypomethylation around WNT1 gene: Implications for solar lentigines

Yamada

Hasegawa

Iwata

et al. 2019

Experimental Dermatology

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Wnt/β‐catenin signalling promotes melanogenesis in melanocytes and also induces melanocytogenesis from melanocyte stem cells (McSCs). Previous study reported that WNT1, a ligand which activates Wnt/β‐catenin signalling pathway, was more highly expressed in the epidermis at SLs than in normal skin areas, suggesting that WNT1 causes hyperpigmentation. To elucidate the mechanism by which WNT1 expression is increased in SLs, we examined the methylation of 5‐carbon of cytosine (5mC), that is 5‐methylcytosine (5mC) level, in a region within the WNT1 promoter; the methylation of the region was known to negatively regulate WNT1 gene expression. We used an immortalized cell line of human interfollicular epidermal stem cells to analyse the effect of UVB irradiation on DNA methylation level of WNT1 promoter and found that UVB irradiation caused demethylation of WNT1 promoter and promoted WNT1 mRNA expression. It was also found that UVB irradiation reduced the expression of DNA methyltransferase 1 (DNMT1), an enzyme responsible for maintaining methylation patterns during cell division. Pathological analysis of SLs and non‐SL regions in the human skin revealed that both DNMT1 expression and 5mC level were decreased at SLs compared to non‐SL skins. Furthermore, bisulphite sequencing showed that the methylated CpG level in WNT1 promoter was also lower at SLs than in non‐SL skins. Thus, in the skin exposed to a high amount of UV rays, excessive expression of WNT1 is thought to be caused by the demethylation of WNT1 promoter, and the upregulated WNT1 promotes melanocytogenesis and melanogenesis, then resulting in SL formation.

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Section: Discussionmentioning

confidence: 56%

UV irradiation‐induced DNA hypomethylation around WNT1 gene: Implications for solar lentigines

Yamada

Hasegawa

Iwata

et al. 2019

Experimental Dermatology

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“…Many critical genes involved in the progression of melanoma from melanocytes have been documented to acquire changes in their methylation. The expression of cyclin‐dependent kinase inhibitor 2A ( CDHN2A ) has been shown to be inactivated by promoter hypermethylation in cutaneous melanoma, which encodes p16 cell cycle inhibitor protein belonging to INK4a/ARE family . The p16 protein inhibits the cell cycle progression through inactivation of CDK‐cyclin complexes.…”

Section: Dna Methylation In Melanomamentioning

confidence: 99%

“…Methylation‐dependent DNA binding proteins (MBDs) spontaneously bind to the hypermethylated sites of the promoter regions, which further assist in silencing of genes by recruiting transcriptional repressor complexes . In addition to the MBDs, methylated regions also bind with histone deacetylases (HDACs) and other chromatin remodeling proteins . HDACs remove the acetyl groups from histone tails which lead to chromatin condensation .…”

Section: Dna Methylation In Melanomamentioning

confidence: 99%

“…In addition to the MBDs, methylated regions also bind with histone deacetylases (HDACs) and other chromatin remodeling proteins . HDACs remove the acetyl groups from histone tails which lead to chromatin condensation . Hypomethylation occurs in the regulatory promoter region of many genes that are involved in cell cycle regulation, invasion, angiogenesis, and metastasis.…”

Section: Dna Methylation In Melanomamentioning

confidence: 99%

“…Guo and co‐workers analyzed 34 primary cutaneous melanoma samples for their global methylation status and observed more than 98% loss of methylation and only about 2% changes were due to the gain of methylation . The aberrant expression of Melanoma antigen, MAGE, by promoter hypomethylation occur in malignant melanoma . Claudin11 (CLDN11) group of genes encode proteins involved in tight junctions.…”

Section: Dna Methylation In Melanomamentioning

confidence: 99%

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Epigenetics of skin cancer: Interventions by selected bioactive phytochemicals

Penta

Somashekar

Meeran

2017

Photoderm Photoimm Photomed

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The prevalence and risk of skin cancer have been increasing over past three decades. Two major types of skin cancer observed in humans are melanoma and nonmelanoma. Nonmelanoma further subdivided into basal cell carcinoma and squamous cell carcinoma. Melanoma arises from melanocyte which locates at the bottom layer of skin epidermis, which primarily protects the skin from being exposed to external factors. Melanoma is less common among all other types of skin cancers but causes higher mortality. Epigenetic regulation associated with the transcriptional activation and inactivation of genes plays a major role in various disease progression including skin cancer. The major epigenetic changes observed at cellular level include DNA methylation, histone modifications, and miRNA-mediated gene regulation. The aberrant pattern in these epigenetic processes leads to altered expression of several genes involved in cell cycle, cell proliferation, cell motility, and apoptosis. Several natural bioactive phytochemicals have been shown to exhibit epigenetic modulatory capability and act as chemopreventive as well as therapeutic agents. In this review, we mainly discuss the major epigenetic modifications observed in melanoma and the epigenetic modulatory role of selected bioactive phytochemicals against the skin cancer.

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Genome‐wide characterization of 5‐hydoxymethylcytosine in melanoma reveals major differences with nevus

Salgado

Oosting

Janssen

et al. 2020

Genes Chromosomes & Cancer

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Melanoma demonstrates altered patterns of DNA methylation that are associated with genetic instability and transcriptional repression of numerous genes. Active DNA demethylation is mediated by TET enzymes that catalyze conversion of 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC). Loss of hmC occurs in melanoma and correlates with disease progression. Here we analyzed the genomic distribution of hmC along with mC in nevus and melanoma using oxidative bisulfite chemistry combined with high-density arrays. HmC was enriched relative to mC at enhancers, 5 0 UTR regions and CpG shores in nevus and melanoma samples, pointing to specific TET enzyme activity. The proportion of interrogated CpG sites with high hmC levels was lower in melanoma (0.54%) than in nevus (2.0%). Depletion of hmC in melanoma was evident across all chromosomes and intragenic regions, being more pronounced in metastatic than in non-metastatic tumors. The patterns of hmC distribution in melanoma samples differed significantly from those in nevus samples, exceeding differences in mC patterns. We identified specific CpG sites and regions with significantly lower hmC levels in melanoma than in nevus that might serve as diagnostic markers. Differentially hydroxymethylated regions localized to cancerrelated genes, including the PTEN gene promoter, suggesting that deregulated DNA hydroxymethylation may contribute to melanoma pathogenesis.

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DNA methylation/hydroxymethylation in melanoma

Cited by 43 publications

References 113 publications

UV irradiation‐induced DNA hypomethylation around WNT1 gene: Implications for solar lentigines

UV irradiation‐induced DNA hypomethylation around WNT1 gene: Implications for solar lentigines

Epigenetics of skin cancer: Interventions by selected bioactive phytochemicals

Genome‐wide characterization of 5‐hydoxymethylcytosine in melanoma reveals major differences with nevus

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