Highlights
- •Cancer is a sickness, initiated and driven via accumulation and interaction of genetic and epigenetic modification of genes involved in regulation of cell communication, signaling and growth division.
- •Epigenetics is known as heritable changes in the expression of genes which are different from mutations that are not attributable to modification of DNA sequence.
- •The role of epigenetics in controlling of gene expression has been considered as a fundamental process in the pathogenesis of a variety of malignancies, for instance reproductive organs cancers.
- •Epigenetic modifications in the tissues of patients affected by cancer are found to provide the promise of novel tumor biomarkers for early diagnosis, prediction, prognosis of cancer, as well as the response to treatment.
- •In the future, pioneering diagnostic methodologies, technologies and treatment regimens will be based on epigenetic mechanisms and may be integrated into the gynecologist's practice.
Abstract
Thyroid cancer remains the highest prevailing endocrine malignancy, and its incidence
rate has progressively increased in the previous years. Above 95% of thyroid tumor
are follicular cells types of carcinoma in which are considered invasive type of tumor.
The pathogenesis and molecular mechanism of thyroid tumors are yet remains elucidated,
in spite of activating RET, RAS and BRAF carcinogenesis have been well introduced.
Nemours molecular alterations have been defined and have revealed promise for their
diagnostic, prognostic and therapeutic capacity but still need further confirmation.
Among different types of mechanisms, the current article reviews the importance of
epigenetic modifications in thyroid cancer. Increasing data from previous reports
demonstrate that acquired epigenetic abnormalities together with genetic changes plays
an important role in alteration of gene expression patterns. Aberrant DNA methylation
has been well known in the CpG regions and profile of microRNAs (mi-RNAs) expression
also involved in cancer development. In addition, the gene expression through epigenetic
control contribution to thyroid cancer is analyzed and it is semi considered in the
clinic. However the epigenetic of the thyroid cancer is yet remains in its early stages,
and it carries encouraging potential thyroid cancer detections in its early stages,
assessment of prognosis and targeted cancer treatment.
Keywords
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References
- Common genetic variation in cellular transport genes and epithelial ovarian cancer (EOC) risk.PLoS One. 2015; 10e0128106
- The interactions of microRNA and epigenetic modifications in prostate cancer.Cancers (Basel). 2013; 5: 998-1019
- Genetic and epigenetic changes in sporadic endocrine tumors: parathyroid tumors.Mol Cell Endocrinol. 2014; 386: 46-54
- DNA methylation and gene silencing in cancer.Nat Clin Pract Oncol. 2005; 2: S4-11
- Detection of underlying characteristics of nuclear chromatin patterns of thyroid tumor cells using texture and factor analyses.Cytometry. 2002; 49: 91-95
- Epigenetics of thyroid cancer and novel therapeutic targets.J Mol Endocrinol. 2011; 46: R73-R81
- Epigenetics: the science of change.Environ Health Perspect. 2006; 114: A160-A167
- Epigenetic responses to environmental change and their evolutionary implications.Philosop. Trans. R Soc B. 2009; 364: 3403-3418
- Epigenetics in cancer.Carcinogenesis. 2010; 31: 27-36
- Epigenetic mutations can both help and hinder adaptive evolution.Mol Ecol. 2015;
- Aberrant epigenetic landscape in cancer: how cellular identity goes awry.Dev. Cell. 2010; 19: 698-711
- Epigenetic regulation of multiple tumor-related genes leads to suppression of breast tumorigenesis by dietary genistein.PLoS One. 2013; 8: e54369
- Epigenetic modifications in human thyroid cancer.Biomed Rep. 2015; 3: 3-8
- Molecular pathogenesis and mechanisms of thyroid cancer.Nat Rev Cancer. 2013; 13: 184-199
- Hallmarks of aromatase inhibitor drug resistance revealed by epigenetic profiling in breast cancer.Cancer Res. 2013; 73: 6632-6641
- New targeted therapies for anaplastic thyroid cancer.Anticancer Agents Med Chem. 2012; 12: 87-93
- The epigenetic regulation of the opioid system: new individualized prompt prevention and treatment strategies.J Cell Biochem. 2015;
- DNA methylation within transcribed regions.Plant Physiol. 2015;
- DNA methylation, methyltransferases, and cancer.Oncogene. 2001; 20: 3139-3155
- Germinal center B-cell-associated DNA hypomethylation at transcriptional regions of the AID gene.Mol. Immunol. 2008; 45: 1712-1719
- Decreased PADI4 mRNA association with global hypomethylation in hepatocellular carcinoma during HBV exposure.Cell Biochem Biophys. 2013; 65: 187-195
- DNA hypomethylation in cancer cells.Epigenomics. 2009; 1: 239-259
- Methylation microarray analysis of late-stage ovarian carcinomas distinguishes progression-free survival in patients and identifies candidate epigenetic markers.Clin Cancer Res. 2002; 8: 2246-2252
- CpG islands and the regulation of transcription.Genes Dev. 2011; 25: 1010-1022
- Promoter hypermethylation of the p16 gene and loss of its protein expression is correlated with tumor progression in extrahepatic bile duct carcinomas.Arch Pathol Lab Med. 2006; 130: 33-38
- Association of aberrant methylation of tumor suppressor genes with tumor aggressiveness and BRAF mutation in papillary thyroid cancer.Int J Cancer. 2006; 119: 2322-2329
- Hypermethylation of the DNA mismatch repair gene hMLH1 and its association with lymph node metastasis and T1799A BRAF mutation in patients with papillary thyroid cancer.Cancer. 2008; 113: 247-255
- DNA hypermethylation of cell cycle (p15 and p16) and apoptotic (p14, p53, DAPK and TMS1) genes in peripheral blood of leukemia patients.Asian Pac J Cancer Prev. 2014; 15: 75-84
- Hypermethylation of carcinogen metabolism genes, CYP1A1, CYP2A13 and GSTM1 genes in head and neck cancer.Oral Dis. 2010; 16: 668-673
- The 3D tissue microenvironment modulates DNA methylation and E-cadherin expression in squamous cell carcinoma.Epigenetics. 2012; 7: 34-46
- MicroRNA role in thyroid cancer pathogenesis.Front Biosci (Landmark Ed). 2013; 18: 734-739
- DNA methylation: roles in mammalian development.Nat Rev Genet. 2013; 14: 204-220
- DNA methylation profiles of human active and inactive X chromosomes.Genome Res. 2011; 21: 1592-1600
- Age-associated DNA methylation changes in immune genes, histone modifiers and chromatin remodeling factors within 5 years after birth in human blood leukocytes.Clin Epigenetics. 2015; 7: 34
- Identification of novel DNA-methylated genes that correlate with human prostate cancer and high-grade prostatic intraepithelial neoplasia.Prostate Cancer Prostatic Dis. 2013; 16: 292-300
- Clinical significance of MLH1 methylation and CpG island methylator phenotype as prognostic markers in patients with gastric cancer.PLoS One. 2015; 10e0130409
- DNA methylation profiling reveals novel biomarkers and important roles for DNA methyltransferases in prostate cancer.Genome Res. 2011; 21: 1017-1027
- Absolute quantification of acetylation and phosphorylation of the histone variant H2AX upon ionizing radiation reveals distinct cellular responses in two cancer cell lines.Radiat Environ Biophys. 2015;
- Histone modifications and nuclear architecture: a review.J Histochem Cytochem. 2008; 56: 711-721
- Regulation of chromatin by histone modifications.Cell Res. 2011; 21: 381-395
- Altered histone modifications in cancer.Adv Exp Med Biol. 2013; 754: 81-107
- Chromatin modifications and DNA repair: beyond double-strand breaks.Front Genet. 2014; 5: 296
- Histone modifications and cancer.Adv. Genet. 2010; 70: 57-85
- Histone modifications and chromatin organization in prostate cancer.Epigenomics. 2010; 2: 551-560
- Histone acetylation and transcriptional regulatory mechanisms.Genes Dev. 1998; 12: 599-606
- Histone deacetylation of NIS promoter underlies BRAF V600E-promoted NIS silencing in thyroid cancer.Endocr Relat Cancer. 2014; 21: 161-173
- New and emerging HDAC inhibitors for cancer treatment.J Clin Invest. 2014; 124: 30-39
- CpG island methylator phenotype-low (CIMP-low) colorectal cancer shows not only few methylated CIMP-high-specific CpG islands, but also low-level methylation at individual loci.Mod Pathol. 2008; 21: 245-255
- Association of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history.Cancer Epidemiol Biomarkers Prev. 2015; 24: 512-519
- An epigenetic signature in peripheral blood predicts active ovarian cancer.PLoS One. 2009; 4: e8274
- SOCS3 promoter hypermethylation is a favorable prognosticator and a novel indicator for G-CIMP-positive GBM patients.PLoS One. 2014; 9: e91829
- The CpG island methylator phenotype and chromosomal instability are inversely correlated in sporadic colorectal cancer.Gastroenterology. 2007; 132: 127-138
- DNA methylation: an alternative pathway to cancer.Ann Surg. 2001; 234: 10-20
- DNA methylation and environmental exposures in human hepatocellular carcinoma.J Natl Cancer Inst. 2002; 94: 755-761
- Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype.Cancer Res. 1999; 59: 5438-5442
- CpG island methylator phenotype redefines the prognostic effect of t(12;21) in childhood acute lymphoblastic leukemia.Clin Cancer Res. 2006; 12: 4845-4850
- Exclusive mutation in epidermal growth factor receptor gene, HER-2, and KRAS, and synchronous methylation of nonsmall cell lung cancer.Cancer. 2006; 106: 2200-2207
- Examination of a CpG island methylator phenotype and implications of methylation profiles in solid tumors.Cancer Res. 2006; 66: 10621-10629
- Primary ovarian carcinomas display multiple methylator phenotypes involving known tumor suppressor genes.Am J Pathol. 2001; 158: 1121-1127
- Aberrantly methylated genes in human papillary thyroid cancer and their association with BRAF/RAS mutation.Front Genet. 2013; 4: 271
- B-RafV600E inhibits sodium iodide symporter expression via regulation of DNA methyltransferase 1.Exp. Mol. Med. 2014; 46: e120
- CpG island methylator phenotype (CIMP) in cancer: causes and implications.Cancer Lett. 2008; 268: 177-186
- CpG island methylator phenotype predicts progression of malignant melanoma.Clin Cancer Res. 2009; 15: 1801-1807
- Identification of candidate epigenetic biomarkers for ovarian cancer detection.Oncol Rep. 2009; 22: 853-861
- Pan-cancer patterns of DNA methylation.Genome Med. 2014; 6: 66
- DNA methylation profiles in ovarian cancer: implication in diagnosis and therapy (Review).Mol Med Rep. 2014; 10: 3-9
- Epigenetics modifications and therapeutic prospects in human thyroid cancer.Front Endocrinol (Lausanne). 2012; 3: 40
- Epigenetic silencing of TTF-1/NKX2-1 through DNA hypermethylation and histone H3 modulation in thyroid carcinomas.Lab Invest. 2009; 89: 791-799
- Quantitative assessment of promoter methylation profiles in thyroid neoplasms.J Clin Endocrinol Metab. 2005; 90: 4011-4018
- Frequent epigenetic silencing of the CpG island promoter of RASSF1A in thyroid carcinoma.Cancer Res. 2002; 62: 3698-3701
- PTEN promoter methylation in sporadic thyroid carcinomas.Thyroid. 2006; 16: 17-23
- New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway.Proc Natl Acad Sci USA. 1999; 96: 4240-4245
- Early occurrence of RASSF1A hypermethylation and its mutual exclusion with BRAF mutation in thyroid tumorigenesis.Cancer Res. 2004; 64: 1664-1668
- A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2.Nat Med. 2003; 9: 407-415
- RET/Papillary thyroid carcinoma oncogenic signaling through the Rap1 Small GTPase.Cancer Res. 2007; 67: 381-390
- Ras-associated protein-1 regulates extracellular signal-regulated kinase activation and migration in melanoma cells: two processes important to melanoma tumorigenesis and metastasis.Cancer Res. 2006; 66: 7880-7888
- Rap1-Mediated activation of extracellular signal-regulated kinases by cyclic amp is dependent on the mode of Rap1 activation.Mol. Cell. Biol. 2006; 26: 2130-2145
- Identification of a putative tumor suppressor gene Rap1GAP in pancreatic cancer.Cancer Res. 2006; 66: 898-906
- Rap1GAP inhibits tumor growth in oropharyngeal squamous cell carcinoma.Am J Pathol. 2006; 168: 585-596
- Loss of Rap1GAP in papillary thyroid cancer.J Clin Endocrinol Metab. 2009; 94: 1026-1032
- Downregulation of Rap1GAP contributes to Ras transformation.Mol Cell Biol. 2007; 27: 6647-6658
- DNA methylation signatures identify biologically distinct thyroid cancer subtypes.J Clin Endocrinol Metab. 2013; 98: 2811-2821
- Levels of histone acetylation in thyroid tumors.Biochem Biophys Res Commun. 2011; 411: 679-683
- Enhancer of zeste homolog 2 overexpression has a role in the development of anaplastic thyroid carcinomas.J Clin Endocrinol Metab. 2011; 96: 1029-1038
- Long non-coding and coding RNA profiling using strand-specific RNA-seq in human hypertrophic cardiomyopathy.Sci Data. 2019; 6 (-90): 90
- cncRNAs: Bi-functional RNAs with protein coding and non-coding functions.Semin. Cell Dev. Biol. 2015; 47-48: 40-51
- Systematic analysis of long non-coding RNAs and mRNAs in the ovaries of Duroc pigs during different follicular stages using RNA sequencing.Int J Mol Sci. 2018; 19: 1722
- Genome-Wide identification of long non-coding RNAs responsive to Lasiodiplodia theobromae infection in Grapevine.Evol Bioinform Online. 2019; 15 (1176934319841362-1176934319841362)
- The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression.Genome Res. 2012; 22: 1775-1789
- Platforms for investigating LncRNA functions.Slas Technol. 2018; 23: 493-506
- Long noncoding RNA transcriptome of plants.Plant Biotechnol. J. 2015; 13: 319-328
- The transcriptional landscape of the mammalian genome.Science. 2005; 309: 1559-1563
- The relationship between non-protein-coding dna and eukaryotic complexity, Bioessays: news and reviews in molecular.Cellular Develop Biol. 2007; 29: 288-299
- Long non-coding RNA and breast cancer.Technol Cancer Res Treat. 2019; 18 (1533033819843889-1533033819843889)
- Long non-coding RNAs in the regulation of gene expression: physiology and disease.Noncoding RNA. 2019; 5: 17
- LncRNA structural characteristics in epigenetic regulation.Int J Mol Sci. 2017; 18: 2659
- Chromatin remodelling and epigenetic state regulation by non-coding RNAs in the diseased heart.Non-Coding RNA Res. 2018; 3: 20-28
- Splicing regulation by long noncoding RNAs.Nucleic Acids Res. 2018; 46: 2169-2184
- The emerging role of lncRNAs in cancer.Nat. Med. 2015; 21: 1253-1261
- Could lncRNAs be the missing links in control of mesenchymal stem cell differentiation?.J. Cell. Physiol. 2015; 230: 526-534
- Analysis of LncRNA expression in cell differentiation.RNA Biol. 2018; 15: 413-422
- Autophagy-Modulating long non-coding RNAs (LncRNAs) and their molecular events in cancer.Front Genet. 2019; 9 (-750): 750
- MIR100 host gene-encoded lncRNAs regulate cell cycle by modulating the interaction between HuR and its target mRNAs.Nucleic Acids Res. 2018; 46: 10405-10416
- lncRNA LINC01296 regulates the proliferation, metastasis and cell cycle of osteosarcoma through cyclin D1.Oncol. Rep. 2018; 40: 2507-2514
- The long non-coding RNA SNHG1 attenuates cell apoptosis by regulating miR-195 and BCL2-Like protein 2 in human cardiomyocytes.Cell Physiol Biochem. 2018; 50: 1029-1040
- The regulatory roles of lncRNAs in the process of breast cancer invasion and metastasis.Biosci Rep. 2018; 38 (BSR20180772)
- Research progresses in roles of LncRNA and its relationships with breast cancer.Cancer Cell Int. 2018; 18 (-179): 179
- Long non-coding RNA in stem cell pluripotency and lineage commitment: functions and evolutionary conservation.Cell Mol Life Sci. 2019; 76: 1459-1471
- Long non-coding RNAs in multifactorial diseases: another layer of complexity.Noncoding RNA. 2018; 4: 13
- Thyroid cancers of follicular origin in a genomic light: in-depth overview of common and unique molecular marker candidates.Mol. Cancer. 2018; 17: 116
- Downregulation of long noncoding RNA NONHSAT037832 in papillary thyroid carcinoma and its clinical significance.Tumour Biol. 2015; 37: 6117-6123
- Integrated analysis of long noncoding RNA interactions reveals the potential role in progression of human papillary thyroid cancer.Cancer Med. 2018; 7: 5394-5410
- Pathway analysis of a genome-wide association study on a long non-coding RNA expression profile in oral squamous cell carcinoma.Oncol. Rep. 2019; 41: 895-907
- Genome-wide analysis of long noncoding RNA expression profile in papillary thyroid carcinoma.Gene. 2015; 569: 109-117
- Long noncoding RNA are aberrantly expressed in human papillary thyroid carcinoma.Oncol Lett. 2016; 12: 544-552
- Identification of specific long non-coding RNA expression: profile and analysis of association with clinicopathologic characteristics and BRAF mutation in papillary thyroid cancer.Thyroid. 2016; 26: 1719-1732
- Long non-coding RNAs in thyroid cancer: implications for pathogenesis, diagnosis, and therapy.Oncol Res Treat. 2019; 42: 136-142
- The role of microRNAs in the proliferation, differentiation, invasion, and apoptosis of trophoblasts during the occurrence of preeclampsia—A systematic review.Tzu Chi Med J. 2015; 27: 54-64
- MicroRNA expression profiles in differentiated thyroid cancer, a review.Int J Clin Exp Med. 2013; 6: 74-80
- MicroRNAs in hepatocellular carcinoma: carcinogenesis, progression, and therapeutic target.Biomed Res Int. 2014; (2014)486407
- MicroRNA and cancer.Mol Oncol. 2012; 6: 590-610
- MicroRNA regulation of tumorigenesis, cancer progression and interpatient heterogeneity: towards clinical use.Genome Biol. 2014; 15: 445
- microRNAs as oncogenes and tumor suppressors.Dev Biol. 2007; 302: 1-12
- MicroRNA signatures in human cancers.Nat Rev Cancer. 2006; 6: 857-866
- new biomarkers in diagnosis, prognosis and treatment of cancer (review).Int J Oncol. 2012; 41: 1897-1912
- MicroRNAs networks in thyroid cancers: focus on miRNAs related to the fascin.J Diabetes Metab Disord. 2013; 12: 31
- Emerging epigenetic targets and therapies in cancer medicine.Cancer Discov. 2012; 2: 405-413
- Developmental pattern of gene-specific dna methylation in the mouse embryo and germ line.Genes Dev. 1992; 6: 705-714
- CpG-island methylation in aging and cancer.Curr Top Microbiol Immunol. 2000; 249: 101-118
- Thyroid cancer: pathogenesis and targeted therapy.Ther Adv Endocrinol Metab. 2011; 2: 173-195
- DNA methylation analysis: a powerful new tool for lung cancer diagnosis.Oncogene. 2002; 21: 5450-5461
- A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer.Nat Genet. 2002; 31: 141-149
- Restoration of iodide uptake in dedifferentiated thyroid carcinoma: relationship to human Na+/I-symporter gene methylation status.J Clin Endocrinol Metab. 1999; 84: 2449-2457
- Methylation of the thyroid-stimulating hormone receptor gene in epithelial thyroid tumors: a marker of malignancy and a cause of gene silencing.Cancer Res. 2003; 63: 2316-2321
- Increased iodine uptake in thyroid carcinoma after treatment with sodium butyrate and decitabine (5-Aza-dC).Otolaryngol Head Neck Surg. 2007; 137: 722-728
- Retinoic acid receptor beta2 re-expression and growth inhibition in thyroid carcinoma cell lines after 5-aza-2′-deoxycytidine treatment.J Endocrinol Invest. 2008; 31: 724-730
- DNA methylation: its role in cancer development and therapy.Curr Probl Cancer. 2008; 32: 187-235
- Histone-deacetylase inhibitors: novel drugs for the treatment of cancer.Nat Rev Drug Discov. 2002; 1: 287-299
- Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B.Mol Cancer Ther. 2003; 2: 971-984
- Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101.Mol Cancer Ther. 2003; 2: 721-728
- Development of the pan-DAC inhibitor panobinostat (LBH589): successes and challenges.Cancer Lett. 2009; 280: 233-241
Article info
Publication history
Published online: August 23, 2019
Accepted:
August 22,
2019
Received in revised form:
July 27,
2019
Received:
March 7,
2019
Identification
Copyright
© 2019 Elsevier Inc. All rights reserved.
