Epigenetic Disregulation in Oral Cancer
Abstract
:1. Introduction
2. Epigenetics
3. DNA Methylation
4. DNA Methylation in Oral Carcinogenesis
4.1. CDKN2A
4.2. E-Cadherin and N-Cadherin
4.3. PTEN
4.4. P53
4.5. DAPK1
4.6. MGMT
4.7. RARB2
4.8. RASSF1 and RASSF2
5. miRNA
6. Chromatin Dynamics and Histones Modifications
7. Human Papilloma Virus (HPV)
8. Considerations
Acknowledgments
References
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Epigenetic change | Putative mechanism | Biological consequence |
---|---|---|
DNA hypomethylation | Activation of cellular oncogenes | Increased proliferation, growth advantage |
Activation of transposable element | Genomic instability, transcriptional noise | |
DNA hypermethylation | De novo hypermethylation of CpG islands within gene promoters leading to silencing of tumor suppressors and cancer-associated genes | Genomic and chromosomal instability, increased proliferation, growth advantage |
Loss of imprinting (LOI) | Reactivation of silent alleles, biallelic expression of imprinted genes | Expansion of precursor cell population |
Relaxation of X-chromosome inactivation | Mechanisms is unknown but it appears to be age-related | Altered gene dosage, growth advantage |
Histone acetylation | Gain-of-function | Activation of tumor promoting genes |
Loss-of-function | Defects in DNA repair and checkpoints | |
Histone deacetylation | Silencing of tumor suppressor genes | Genomic instability, increased proliferation |
Histone methylation | Loss of heritable patterns of gene expression (“cellular memory”) | Genomic instability, growth advantage |
MicroRNAs (miRNAs) amplification in cancer | Function as oncogenes | Neoplastic transformation |
MicroRNAs (miRNAs) deletion in cancer | Function as tumor suppressors. | Neoplastic transformation |
Gene | Locus | Function | Alterations | Ref |
---|---|---|---|---|
ABO | 9q34 | Blood group antigen | Hypermethilation | 34 |
APC | 5q21 | Signal transduction | Hypermethilation | 33,35 |
ATM | 11q22-q23 | Tumor suppressor | Hypermethilation | 4,30,36,37 |
C/EBPα | 19q13 | Tumor suppressor | Hypermethilation | 38 |
CDKN2A | 9p21 | Cell cycle | LOH, hypermethilation | 4,39 |
CRABP2 | 1q21 | Nuclear transcriptional regulator | Hypermethilation | 40 |
DAPK | 9q | Apoptosis | Hypermethilation | 4,30,32,34,35,37 |
DCC | 18q21 | Tumor suppressor | Hypermethilation | 4,30,34,37 |
DKK3 | 11p | Transcriptional regulator | Hypermethilation | 12 |
E-cadherin | 16q22 | Signal transduction | Hypermethilation | 4,32,41,42,34,36 |
EDNRB | 13q22 | Signal transduction | Hypermethilation | 39 |
GSTP1 | 11q13 | Detoxification of carcinogens | Hypermethilation | 30,43 |
H3K4 | 1q21.2 | Histone | Hypermethilation | 44 |
HIN1 | 12p13 | Tumor suppressor | Hypermethilation | 45 |
Hmlh1 | 3p21 | DNA repair | Hypermethilation | 30,32,34 36 |
LHX6 | 9q33 | Transcriptional regulator | Hypermethilation | 38 |
MGMT | 10q26 | DNA repair | Hypermethilation | 4,30,32,41,35,37 |
MINT family | / | / | Hypermethilation | 30 |
miR137 | 1p21.3 | Tumor suppressor | Hypermethilation | 46 |
miR193a | 17q11.2 | Tumor suppressor | Hypermethilation | 46 |
MX1 | 21q22 | / | Hypermethilation | 40 |
p14 | 9p21 | Apoptosis | LOH, hypermethilation | 30,34 |
p15 | 9p21 | Cell cycle | LOH, deletion, mutation, hypermethilation | 4,37 |
p16 | 9p21 | Cell cycle | LOH, mutation, deletion, hypermethilation | 30,32,35 38 |
p53 | 17p13 | Tumor suppressor | Mutation, hypermethilation | 30 |
p73 | 1p36 | Apoptosis | Hypermethilation | 30,34,35,38 |
PTEN | 10q23 | Tumor suppressor | Hypermethilation | 47 50 |
RARB2 | 17q21 | Nuclear transcriptional Regulator | Hypermethilation | 4,30,42,34,35,37 |
RASSF-1 | 3p21 | Apoptosis | Hypermethilation | 4,32,51,37 |
Rb | 13q14 | Tumor suppressor | Hypermethilation, mutation | 35 |
RUNX3 | 1p36 | Transcriptional regulator | Hypermethilation | 32,39 |
SFRP1 | 8p11.21 | Transcriptional regulator | Hypometilation | 52 |
SFRP1-2-4-5 | 8p11.21 4q31.3 7p14.1 10q24.1 | Transcriptional regulator | Hypermethilation | 52,38,53 |
TCF21 | 6q23-q24 | epithelial-mesenchymal interactions | Hypermethilation | 38 |
THBS1 | 15q15 | cell-to-cell and cell-to-matrix interactions | Hypermethilation | 35 |
TIMP3 | 22q12 | epithelial-mesenchymal interactions | Hypermethilation | 4,37 |
WIF1 | 12q14 | Transcriptional regulator | Hypermethilation | 32,52 |
σ-14-3-3 | 1p36 | Signal transduction | Hypermethilation | 30,34 |
Cellular function | microRNAs | Expression in OSCC |
---|---|---|
Proliferation and apoptosis | miR-137, miR-193a, miR-133a, miR-133b, miR-503, miR-15a | Down-regulated |
miR-21, miR-24 and miR-184 | Up-regulated | |
Metastasis | miR-222 and miR-138 | Down-regulated |
miR-211 and miR-31 | Up-regulated | |
Chemoresistance | miR-21 | Down-regulated |
miR-23a, miR-214, miR-98 | Up-regulated |
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
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Mascolo, M.; Siano, M.; Ilardi, G.; Russo, D.; Merolla, F.; Rosa, G.D.; Staibano, S. Epigenetic Disregulation in Oral Cancer. Int. J. Mol. Sci. 2012, 13, 2331-2353. https://doi.org/10.3390/ijms13022331
Mascolo M, Siano M, Ilardi G, Russo D, Merolla F, Rosa GD, Staibano S. Epigenetic Disregulation in Oral Cancer. International Journal of Molecular Sciences. 2012; 13(2):2331-2353. https://doi.org/10.3390/ijms13022331
Chicago/Turabian StyleMascolo, Massimo, Maria Siano, Gennaro Ilardi, Daniela Russo, Francesco Merolla, Gaetano De Rosa, and Stefania Staibano. 2012. "Epigenetic Disregulation in Oral Cancer" International Journal of Molecular Sciences 13, no. 2: 2331-2353. https://doi.org/10.3390/ijms13022331