42
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Epigenetic regulation in human melanoma: past and future

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The development and progression of melanoma have been attributed to independent or combined genetic and epigenetic events. There has been remarkable progress in understanding melanoma pathogenesis in terms of genetic alterations. However, recent studies have revealed a complex involvement of epigenetic mechanisms in the regulation of gene expression, including methylation, chromatin modification and remodeling, and the diverse activities of non-coding RNAs. The roles of gene methylation and miRNAs have been relatively well studied in melanoma, but other studies have shown that changes in chromatin status and in the differential expression of long non-coding RNAs can lead to altered regulation of key genes. Taken together, they affect the functioning of signaling pathways that influence each other, intersect, and form networks in which local perturbations disturb the activity of the whole system. Here, we focus on how epigenetic events intertwine with these pathways and contribute to the molecular pathogenesis of melanoma.

          Related collections

          Most cited references126

          • Record: found
          • Abstract: found
          • Article: not found

          Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a.

          Expression of the INK4b/ARF/INK4a tumor suppressor locus in normal and cancerous cell growth is controlled by methylation of histone H3 at lysine 27 (H3K27me) as directed by the Polycomb group proteins. The antisense noncoding RNA ANRIL of the INK4b/ARF/INK4a locus is also important for expression of the protein-coding genes in cis, but its mechanism has remained elusive. Here we report that chromobox 7 (CBX7) within the polycomb repressive complex 1 binds to ANRIL, and both CBX7 and ANRIL are found at elevated levels in prostate cancer tissues. In concert with H3K27me recognition, binding to RNA contributes to CBX7 function, and disruption of either interaction impacts the ability of CBX7 to repress the INK4b/ARF/INK4a locus and control senescence. Structure-guided analysis reveals the molecular interplay between noncoding RNA and H3K27me as mediated by the conserved chromodomain. Our study suggests a mechanism by which noncoding RNA participates directly in epigenetic transcriptional repression. Copyright (c) 2010 Elsevier Inc. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene.

            A 42 kb region on human chromosome 9p21 encodes for three distinct tumor suppressors, p16(INK4A), p14(ARF) and p15(INK4B), and is altered in an estimated 30-40% of human tumors. The expression of the INK4A-ARF-INK4B gene cluster is silenced by polycomb during normal cell growth and is activated by oncogenic insults and during aging. How the polycomb is recruited to repress this gene cluster is unclear. Here, we show that expression of oncogenic Ras, which stimulates the expression of p15(INK4B) and p16(INK4A), but not p14(ARF), inhibits the expression of ANRIL (antisense non-coding RNA in the INK4 locus), a 3.8 kb-long non-coding RNA expressed in the opposite direction from INK4A-ARF-INK4B. We show that the p15(INK4B) locus is bound by SUZ12, a component of polycomb repression complex 2 (PRC2), and is H3K27-trimethylated. Notably, depletion of ANRIL disrupts the SUZ12 binding to the p15(INK4B) locus, increases the expression of p15(INK4B), but not p16(INK4A) or p14(ARF), and inhibits cellular proliferation. Finally, RNA immunoprecipitation demonstrates that ANRIL binds to SUZ12 in vivo. Collectively, these results suggest a model in which ANRIL binds to and recruits PRC2 to repress the expression of p15(INK4B) locus.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Polycomb silencers control cell fate, development and cancer.

              Polycomb group (PcG) proteins are epigenetic gene silencers that are implicated in neoplastic development. Their oncogenic function might be associated with their well-established role in the maintenance of embryonic and adult stem cells. In this review, we discuss new insights into the possible mechanisms by which PcGs regulate cellular identity, and speculate how these functions might be relevant during tumorigenesis.
                Bookmark

                Author and article information

                Journal
                Epigenetics
                Epigenetics
                KEPI
                Epigenetics
                Taylor & Francis
                1559-2294
                1559-2308
                February 2015
                14 January 2015
                : 10
                : 2
                : 103-121
                Affiliations
                [1 ]Auckland Cancer Society Research Center; University of Auckland ; Auckland, New Zealand
                [2 ]Molecular Medicine and Pathology; University of Auckland ; Auckland, New Zealand
                Author notes
                Article
                1003746
                10.1080/15592294.2014.1003746
                4622872
                25587943
                29bc724a-db4b-4ba2-94e6-f3e26d95e80d
                © 2015 The Author(s). Published with license by Taylor & Francis Group, LLC© Debina Sarkar, Euphemia Y Leung, Bruce C Baguley, Graeme J Finlay, and Marjan E Askarian-Amiri

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                : 30 October 2014
                : 16 December 2014
                : 26 December 2014
                Page count
                Figures: 3, Tables: 4, References: 167, Pages: 19
                Categories
                Review

                Genetics
                chromatin modification,chromatin remodeling,dna methylation/demethylation,epigenetics,gene regulation,melanoma,ncrnas

                Comments

                Comment on this article