Aberrant DNA methylation in malignant melanoma

Schinke, Carolina; Mo, Yongkai; Yu, Yiting; Amiri, Kathy; Sosman, Jeff; Greally, John M.; Verma, Amit

doi:10.1097/cmr.0b013e328338a35a

Cited by 90 publications

(79 citation statements)

References 99 publications

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“…These results are consistent with an epigenetic mechanism for miR-205 downregulation, and methylation is a well-documented mechanism of aberrant gene expression in melanoma. 55 In addition, distinct sets of chromosomal gains and losses have been described in melanoma and are an attractive mechanism for reproducible alterations of global miRNA expression. However, the 1q32 locus was not reported as a commonly deleted region in large-scale comparative genomic hybridization studies of various subtypes of melanoma.…”

Section: Discussionmentioning

confidence: 99%

Loss of microRNA-205 expression is associated with melanoma progression

Liu

Tetzlaff

Liu

et al. 2012

Laboratory Investigation

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In this study, we used formalin-fixed paraffin-embedded melanocytic tumors to demonstrate reproducible alterations in microRNA expression in nevi compared with melanomas using a microarray platform. We validated those results in an independent set of nevi and melanomas by quantitative RT-PCR. miR-205 demonstrated a statistically significant, progressive diminution in expression from nevi to primary melanomas to metastatic melanomas. Enforced miR-205 expression in melanoma cells profoundly impairs cell motility and migration along with significantly decreased F-actin polymerization with only a modest reduction in cell proliferation. Using a xenograft model, melanoma cells overexpressing miR-205 exhibit a reduced migratory capacity compared with control tumor cells. Mechanistically, miR-205 overexpression results in decreased expression of the zinc-finger E-box binding homeobox 2 (ZEB2) mRNA and protein.This coincides with increased expression of E-cadherin mRNA and protein. Furthermore, re-introduction of ZEB2 into melanoma cells overexpressing miR-205 rescues these phenotypic effects and results in a restoration of cell migration and F-actin polymerization with a concomitant reduction in E-cadherin expression. Together, these results provide in vitro and in vivo evidence for miR-205 as a critical suppressor of melanoma cell migration.

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Section: Discussionmentioning

confidence: 99%

Loss of microRNA-205 expression is associated with melanoma progression

Liu

Tetzlaff

Liu

et al. 2012

Laboratory Investigation

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“…In addition to histone modifications, DNA methylation is also one of the mechanisms for the epigenetic control of gene expression, and aberrant DNA methylation patterns of CpG islands can influence normal transcriptional regulation [80]. The epigenetic regulation of DNA methylation in DR has seldom been reported.…”

Section: Epigenetic Mechanisms In Drmentioning

confidence: 99%

Epigenetic Mechanisms in the Pathogenesis of Diabetic Retinopathy

Zeng

Chen²

2014

Ophthalmologica

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Diabetic retinopathy (DR), which arises as a result of an increasing incidence of diabetes mellitus, has gradually become a common disease. Due to its complex pathogenesis, the treatment means of DR are very limited. The findings of several studies have shown that instituting tight glycemic control in diabetic patients does not immediately benefit the progression of retinopathy, and the benefits of good control persist beyond the period of good glycemic control. This has led to the concept of persistent epigenetic changes. Epigenetics has now become an increasingly important area of biomedical research. Recently, important roles of various epigenetic mechanisms have been identified in the pathogenesis of diabetes and its complications. The aim of this review is to provide an overview of the epigenetics and epigenetic mechanisms in diabetes and diabetes complications, and the focus is on the emerging evidence for aberrant epigenetic mechanisms in DR.

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“…Different epigenetic biomarkers have been described as presenting clinical relevance in different tumor types, such as gliomas, neuroblastomas, leukemias, prostate, bladder, lung, and colorectal cancer (Taby & Issa, 2010). However, very few data are available concerning both diagnosis/prognosis markers and the predictive value of markers in response to therapy in melanoma (Howell et al, 2009;Schinke et al, 2010). A promising predictive marker of melanoma progression was that reported by Mori and coworkers (2006), in which estrogen receptor A (ER-A) methylation was showed as a poor prognostic factor for melanoma patients.…”

Section: Epigenetic Tumor Markersmentioning

confidence: 99%