Review
Epigenetic modifications in colorectal cancer: Molecular insights and therapeutic challenges

https://doi.org/10.1016/j.bbadis.2014.02.006Get rights and content
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Highlights

  • Epigenetic modifications are responsible for aberrant gene expression in cancer.

  • Epigenetics are involved in various aspects of colorectal carcinogenesis.

  • Biomarkers based on DNA methylation gene patterns are already clinically available.

  • Epigenetics offer alternative rational therapeutic targets in solid tumors.

Abstract

Colorectal cancer, a leading cause of mortality worldwide, is a multistep disorder that results from the alteration of genetic and epigenetic mechanisms under contextual influence. Epigenetic aberrations, including DNA methylation, histone modifications, chromatin remodeling and non-coding RNAs, affect every aspect of tumor development from initiation to metastasis. Cancer stem cell promotion is also included in the wide spectrum of epigenetic dysregulations. Elucidation of this complex crosstalk network may offer new insights in the molecular interactions involved in the pathogenesis of colorectal carcinogenesis. In the era of translational medicine new horizons are opened for the pursuit of personalized therapeutic approaches and the development of novel and accurate diagnostic, prognostic and therapy-assessment markers. This review discusses the implications of epigenetic mechanisms in tumor biology and their applications “from bench to bedside”.

Abbreviations

5-FU
fluorouracil
A
acetyl-groups
ALDH1
aldehyde dehydrogenase-1
AP-1
activator protein 1
APC
adenomatous polyposis coli
ASO
anti-sense oligonucleotides
Bmi1
B lymphoma Mo-MLV insertion region 1 homolog
BMP
bone morphogenetic protein
CSC
cancer stem cell
CBP
CREB-binding protein
CDH1
cadherin-1
CDKN2A
cyclin-dependent kinase inhibitor 2A
CDX1
caudal type homeobox-1
CGI
CpG islands
CIMP
CpG island methylator phenotype
CIN
chromosomal instability
CpG
cytosine guanine
CRC
colorectal cancer
DNMT
DNA methyltransferase
DNMTi
DNMT inhibitor
EGCG
epigallocatechin 3-gallate
ERK
extracellular signal-regulated kinase
EZH2
histone methyltransferase enhancer of Zeste 2
FDA
Food and Drug Administration
H
histone
HAT
histone acetyltransferases
HDAC
histone deacetylase
HDACi
HDAC inhibitor
HDMT
histone demethylases
HIF
hypoxia inducible factor
HMT
histone methyltransferase
HOTAIR
hox transcript antisense intergenic RNA
IGF2
insulin-like growth factor-2
K
lysine residue
KLF4
kruppel-like factor 4
linc
long intergenic non-coding
LINE
long interspersed nuclear element
LOI
loss of imprinting
me
methylation
LRES
long range epigenetic silencing
LSD1
lysine specific demethylase 1
me
methylation
MGMT
O-6-methylguanine-DNA methyltransferase
MLL4
mixed lineage leukemia-4
miRNA/miR
microRNA
MSI
microsatellite instability
MTD
maximum tolerated dose
NRF1
nuclear respiratory factor 1
NuRD
nucleosome remodeling and histone deacetylase
PCAF
(CBP)/p300 associated factor
PFS
progression-free survival
PI3K
phosphatidylinositide 3-kinase
PPARδ
peroxisome proliferator activated receptor δ
PRC
polycomb repressive complex
PTEN
phosphatase and tensin homolog
RUNX3
runt-related transcription factor 3
SAM
S-adenosyl-methionide
SEPT9
septin 9
VEGF
vascular endothelial growth factor
YY1
yin yang 1
ZEB
zinc finger E-box-binding homeobox

Keywords

Colorectal cancer
Epigenetics
Histone modification
DNA methylation
Therapy
Prognosis

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These authors made equal contributions.