Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8324605 | The International Journal of Biochemistry & Cell Biology | 2012 | 14 Pages |
Abstract
Epigenetic regulation of gene expression has provided colorectal cancer (CRC) pathogenesis with an additional trait during the past decade. In particular, histone post-translational modifications set up a major component of this process dictating chromatin status and recruiting non-histone proteins in complexes formed to “handle DNA”. In CRC, histone marks of aberrant acetylation and methylation levels on specific residues have been revealed, along with a plethora of deregulated enzymes that catalyze these reactions. Mutations, deletions or altered expression patterns transform the function of several histone-modifying proteins, further supporting the crucial role of epigenetic effectors in CRC oncogenesis, being closely associated to inactivation of tumor suppressor genes. Elucidation of the biochemical basis of these new tumorigenic mechanisms allows novel potential prognostic factors to come into play. Moreover, the detection of these changes even in early stages of the multistep CRC process, along with the reversible nature of these mechanisms and the technical capability to detect such alterations in cancer cells, places this group of covalent modifications as a further potential asset for clinical diagnosis or treatment of CRC. This review underlines the biochemistry of histone modifications and the potential regulatory role of histone-modifying proteins in CRC pathogenesis, to date. Furthermore, the underlying mechanisms of the emerging epigenetic interplay along with the chemical compounds that are candidates for clinical use are discussed, offering new insights for further investigation of key histone enzymes and new therapeutic targets.
Keywords
SUZ12MREscdc2EEDCARM1RUNX3VEGFR1Wnt10bDNA methyltransferasesPCAFmiRNA response elementscompetitive endogenous RNAsRIZ15FULSD1Hox transcript antisense intergenic RNAEZH2DNMTsZEB1PRDMCCAAT enhancer-binding proteinhistone-lysine N-methyltransferasezinc finger E-box-binding homeobox 1N-myc downstream-regulated gene 1XAF115-lipoxygenase-1PSMD9Suv39h1Sirt115-LOX-1TIMP3DMAP1NDRG1APAF1PIK3CBHMTsG9aTSAncRNAsMSICBPMecp2APCPPARγMLH1SAHAmiRNAssirtuin 1HDACsSMYD3NF-κBKLF4C/EBPHDMsMutL homolog 1Small interfering RNAnon-coding RNAssiRNAadenomatous polyposis coliArginineHistone acetylationSuberoylanilide hydroxamic acidlysine-specific demethylase 1Epigeneticsepithelial to mesenchymal transitionMicrosatellite instabilityTrichostatin Aenhancer of zeste homolog 2TumorigenesisEMTmicroRNAsColorectal cancerceRNAsP300/CBP-associated factorapoptotic protease activating factor 1Krüppel-like factor 4Runt-related transcription factor 3nuclear factor kappa Bphosphatase and tensin homolog5-fluorouracilTRAILLysinetumor necrosis factor-related apoptosis-inducing ligandMethylationTissue inhibitor of metalloproteinase 3HOTAIRHistone demethylaseshistone deacetylaseshistone acetyltransferaseshistone methyltransferasesmethyl-CpG-binding protein 2PtenHATsPeroxisome proliferator-activated receptor gammavascular endothelial growth factor receptor 1
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Authors
Antonios N. Gargalionis, Christina Piperi, Christos Adamopoulos, Athanasios G. Papavassiliou,