Journal
MOLECULAR ASPECTS OF MEDICINE
Volume 69, Issue -, Pages 73-92Publisher
ELSEVIER
DOI: 10.1016/j.mam.2019.04.002
Keywords
Colorectal cancer; Epigenetics; DNA methylation; Histone modifications; Chromatin remodeling; miRNA; Prognosis; Epithelial-to-mesenchymal transition; Stemness
Funding
- COST (European Cooperation in Science and Technology) [CA17118]
- Internal Grant Agency of the Ministry of Health of the Czech Republic [NV18-03-00199, AZV 17-30920A]
- Spanish Ministry of Health, Plan Nacional de I+D+I, ISCIII, FEDER [PI18/01484]
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Colorectal carcinogenesis is a multistep process involving the accumulation of genetic alterations over time that ultimately leads to disease progression and metastasis. Binding of transcription factors to gene promoter regions alone cannot explain the complex regulation pattern of gene expression during this process. It is the chromatin structure that allows for a high grade of regulatory flexibility for gene expression. Posttranslational modifications on histone proteins such as acetylation, methylation, or phosphorylation determine the accessibility of transcription factors to DNA. DNA methylation, a chemical modification of DNA that modulates chromatin structure and gene transcription acts in concert with these chromatin conformation alterations. Another epigenetic mechanism regulating gene expression is represented by small non-coding RNAs. Only very recently epigenetic alterations have been included in molecular subtype classification of colorectal cancer (CRC). In this chapter, we will provide examples of the different epigenetic players, focus on their role for epithelial-mesenchymal transition and metastatic processes and discuss their prognostic value in CRC.
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