Promoter Methylation of Tumor Suppressors in Thyroid Carcinoma: A Systematic Review
-
Sara Sheikkholeslami
,
Marjan Zarif -Yeganeh
,
Samaneh Farashi
,
Fereidoun Azizi
,
Sima Kheradmand Kia
,
Ladan Teimoori-Toolabi
,
Mehdi Hedayati
Abstract
Background: The tumor suppressor genes play a critical role in cellular and molecular mechanisms such as cell cycle processes, cell differentiation and apoptosis. Aberrant DNA methylation of tumor suppressor genes and subsequent gene expression changes have shown to be involved in the initiation and progression of various malignancies including thyroid malignancies. In this review, we investigated what is known about the impact of promoter hypermethylation on the key tumor suppressor genes known to be involved in cell growth and/or apoptosis of thyroid cancer.
Methods: The most important databases were searched for research articles until June 2020 to identify reported tumor suppressor genes that are modulated by methylation modulation changes in thyroid carcinoma. Following the inclusion and exclusion criteria, 26 studies were reviewed using the full text to meet the inclusion and exclusion criteria.
Results: The tumor suppressor genes reviewed here are suggestive biomarkers and potential targetable drugs. Inactivation of RASSF1A, DAPK1, SLCFA8, and TSHR through aberrant epigenetic methylation could activate BRAF/MEK/ERK kinase pathways with potential clinical implications in thyroid cancer patients. RARβ2 and RUNX3 could suppress cell cycle and induce apoptosis in malignant cells. TIMP3 and PTEN could prevent angiogenesis and invasion through PIP3 pathway and arrest VEFG activity.
Conclusion: The methylation status of key genes in various types of thyroid malignancies could be used in early diagnosis as well as differentiation of malignant and benign thyroid. This is valuable in drug repurposing and discovering alternative treatments or preventions in thyroid cancer.
1. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM (2014). Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res, 74(11):2913-21.
2. Smith JA, Fan CY, Zou C, Bodenner D, Kokoska MS (2007). Methylation status of genes in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg, 133(10):1006-11.
3. Stephen JK, Chitale D, Narra V, Chen KM, Sawhney R, Worsham MJ (2011). DNA methylation in thyroid tumorigenesis. Cancers (Basel), 3(2):1732-43.
4. Hedayati M, Nozhat Z, Hannani M (2016). Can the Serum Level of Myostatin be Considered as an Informative Factor for Cachexia Prevention in Patients with Medullary Thyroid Cancer? Asian Pac J Cancer Prev, 17(S3):119-23.
5. Qiang W, Zhao Y, Yang Q, et al (2014). ZIC1 is a putative tumor suppressor in thyroid cancer by modulating major signaling pathways and transcription factor FOXO3a. J Clin Endocrinol Metab, 99(7):E1163-72.
6. Stephen JK, Chen KM, Merritt J, Chitale D, Divine G, Worsham MJ (2018). Methylation markers differentiate thyroid cancer from benign nodules. J Endocrinol Invest, 41(2):163-70.
7. Hu S, Liu D, Tufano RP, et al (2006). Association of aberrant methylation of tumor suppressor genes with tumor aggressiveness and BRAF mutation in papillary thyroid cancer. Int J Cancer, 119(10):2322-9.
8. Xing M (2007). Gene methylation in thyroid tumorigenesis. Endocrinology, 148(3):948-53.
9. Lal G, Padmanabha L, Smith BJ, et al (2006). RIZ1 is epigenetically inactivated by promoter hypermethylation in thyroid carcinoma. Cancer, 107(12):2752-9.
10. Schagdarsurengin U, Gimm O, Dralle H, Hoang-Vu C, Dammann R (2006). CpG island methylation of tumor-related promoters occurs preferentially in undifferentiated carcinoma. Thyroid, 16(7):633-42.
11. Kanehisa M, Sato Y, Furumichi M, Morishima K, Tanabe M (2019). New approach for understanding genome variations in KEGG. Nucleic Acids Res, 47(D1):D590-d5.
12. Nikitin A, Egorov S, Daraselia N, Mazo I (2003). Pathway studio--the analysis and navigation of molecular networks. Bioinformatics, 19(16):2155-7.
13. Jiang JL, Tian GL, Chen SJ, Xu LI, Wang HQ (2015). Promoter methylation of p16 and RASSF1A genes may contribute to the risk of papillary thyroid cancer: A meta-analysis. Exp Ther Med, 10(4):1549-55.
14. Wang P, Pei R, Lu Z, Rao X, Liu B (2013). Methylation of p16 CpG islands correlated with metastasis and aggressiveness in papillary thyroid carcinoma. J Chin Med Assoc, 76(3):135-9.
15. Ben-Ari Fuchs S, Lieder I, Stelzer G, et al (2016). GeneAnalytics: An Integrative Gene Set Analysis Tool for Next Generation Sequencing, RNAseq and Microarray Data. Omics, 20(3):139-51.
16. Kamb A, Gruis NA, Weaver-Feldhaus J, et al (1994). A cell cycle regulator potentially involved in genesis of many tumor types. Science, 264(5157):436-40.
17. Elisei R, Shiohara M, Koeffler HP, Fagin JA (1998). Genetic and epigenetic alterations of the cyclin-dependent kinase inhibitors p15INK4b and p16INK4a in human thyroid carcinoma cell lines and primary thyroid carcinomas. Cancer, 83(10):2185-93.
18. Boltze C, Zack S, Quednow C, Bettge S, Roessner A, Schneider-Stock R (2003). Hypermethylation of the CDKN2/p16INK4A promotor in thyroid carcinogenesis. Pathol Res Pract, 199(6):399-404.
19. Lam AK, Lo CY, Leung P, Lang BH, Chan WF, Luk JM (2007). Clinicopathological roles of alterations of tumor suppressor gene p16 in papillary thyroid carcinoma. Ann Surg Oncol, 14(5):1772-9.
20. Mohammadi-asl J, Larijani B, Khorgami Z, et al (2011). Qualitative and quantitative promoter hypermethylation patterns of the P16, TSHR, RASSF1A and RARβ2 genes in papillary thyroid carcinoma. Med Oncol, 28(4):1123-8.
21. Wu W, Yang SF, Liu FF, Zhang JH (2015). Association between p16 Promoter Methylation and Thyroid Cancer Risk: A Meta-analysis. Asian Pac J Cancer Prev, 16(16):7111-5.
22. Donninger H, Vos MD, Clark GJ (2007). The RASSF1A tumor suppressor. J Cell Sci, 120(Pt 18):3163-72.
23. Xing M, Cohen Y, Mambo E, et al (2004). Early occurrence of RASSF1A hypermethylation and its mutual exclusion with BRAF mutation in thyroid tumorigenesis. Cancer Res, 64(5):1664-8.
24. Schagdarsurengin U, Gimm O, Hoang-Vu C, Dralle H, Pfeifer GP, Dammann R (2002). Frequent epigenetic silencing of the CpG island promoter of RASSF1A in thyroid carcinoma. Cancer Res, 62(13):3698-701.
25. Khatami F, Larijani B, Heshmat R, Nasiri S, Haddadi-Aghdam M, Teimoori-Toolabi L (2020). Hypermethylated RASSF1 and SLC5A8 promoters alongside BRAF(V600E) mutation as biomarkers for papillary thyroid carcinoma, J Cell Physiol, 235(10):6954-6968.
26. Hoque MO, Rosenbaum E, Westra WH, et al (2005). Quantitative assessment of promoter methylation profiles in thyroid neoplasms. J Clin Endocrinol Metab, 90(7):4011-8.
27. Shou F, Xu F, Li G, et al (2017). RASSF1A promoter methylation is associated with increased risk of thyroid cancer: a meta-analysis. Onco Targets Ther, 10:247-57.
28. Saavedra HI, Knauf JA, Shirokawa JM, et al (2000). The RAS oncogene induces genomic instability in thyroid PCCL3 cells via the MAPK pathway. Oncogene, 19(34):3948-54.
29. Schagdarsurengin U, Richter AM, Wohler C, Dammann RH (2009). Frequent epigenetic inactivation of RASSF10 in thyroid cancer. Epigenetics, 4(8):571-6.
30. Schagdarsurengin U, Richter AM, Hornung J, Lange C, Steinmann K, Dammann RH (2010). Frequent epigenetic inactivation of RASSF2 in thyroid cancer and functional consequences. Mol Cancer, 9:264.
31. Ganapathy V, Gopal E, Miyauchi S, Prasad PD (2005). Biological functions of SLC5A8, a candidate tumour suppressor. Biochem Soc Trans, 33(Pt 1):237-40.
32. Li H, Myeroff L, Smiraglia D, et al (003). SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc Natl Acad Sci U S A, 100(14):8412-7.
33. Park JY, Kim D, Yang M, et al (2013). Gene silencing of SLC5A8 identified by genome-wide methylation profiling in lung cancer. Lung Cancer, 79(3):198-204.
34. Babu E, Ramachandran S, Coothan Kandaswamy V, et al (2011). Role of SLC5A8, a plasma membrane transporter and a tumor suppressor, in the antitumor activity of dichloroacetate. Oncogene, 30(38):4026-37.
35. Kiseljak-Vassiliades K, Xing M (2011). Association of Cigarette Smoking with Aberrant Methylation of the Tumor Suppressor Gene RARbeta2 in Papillary Thyroid Cancer. Front Endocrinol (Lausanne), 2:99.
36. Zane M, Agostini M, Enzo MV, et al (2013). Circulating cell-free DNA, SLC5A8 and SLC26A4 hypermethylation, BRAF(V600E): A non-invasive tool panel for early detection of thyroid cancer. Biomed Pharmacother, 67(8):723-30.
37. Brait M, Loyo M, Rosenbaum E, et al (2012). Correlation between BRAF mutation and promoter methylation of TIMP3, RARbeta2 and RASSF1A in thyroid cancer. Epigenetics, 7(7):710-9.
38. Connolly RM, Nguyen NK, Sukumar S (2013). Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment. Clin Cancer Res, 19(7):1651-9.
39. Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K (2017). KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res, 45(D1):D353-d61.
40. Qi JH, Ebrahem Q, Moore N, et al (2003). A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med, 9(4):407-15.
41. Schneider-Stock R, Roessner A, Ullrich O (2005). DAP-kinase--protector or enemy in apoptotic cell death. Int J Biochem Cell Biol, 37(9):1763-7.
42. Brueckl WM, Grombach J, Wein A, et al (2005). Alterations in the tissue inhibitor of metalloproteinase-3 (TIMP-3) are found frequently in human colorectal tumours displaying either microsatellite stability (MSS) or instability (MSI). Cancer Lett, 223(1):137-42.
43. Darnton SJ, Hardie LJ, Muc RS, Wild CP, Casson AG (2005). Tissue inhibitor of metalloproteinase-3 (TIMP-3) gene is methylated in the development of esophageal adenocarcinoma: loss of expression correlates with poor prognosis. Int J Cancer, 115(3):351-8.
44. van der Velden PA, Zuidervaart W, Hurks MH, et al (2003). Expression profiling reveals that methylation of TIMP3 is involved in uveal melanoma development. Int J Cancer, 106(4):472-9.
45. Slenter DN, Kutmon M, Hanspers K, et al (2018). WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research. Nucleic Acids Res, 46(D1):D661-d7.
46. Maitland ML, Lou XJ, Ramirez J, et al (2010). Vascular endothelial growth factor pathway. Pharmacogenet Genomics, 20(5):346-9.
47. Whirl-Carrillo M, McDonagh EM, Hebert JM, et al (2012). Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther, 92(4):414-7.
48. Szkudlinski MW, Fremont V, Ronin C, Weintraub BD (2002). Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships. Physiol Reviews, 82(2):473-502.
49. Khan MS, Pandith AA, Masoodi SR, Wani KA, Ul Hussain M, Mudassar S (2014). Epigenetic silencing of TSHR gene in thyroid cancer patients in relation to their BRAF V600E mutation status. Endocrine, 47(2):449-55.
50. Kartal K, Onder S, Kosemehmetoglu K, Kilickap S, Tezel YG, Kaynaroglu V (2015). Methylation status of TSHr in well-differentiated thyroid cancer by using cytologic material. BMC Cancer, 15:824.
51. Qu M, Wan S, Ren B, Wu H, Liu L, Shen H (2020). Association between TSHR gene methylation and papillary thyroid cancer: a meta-analysis. Endocrine, 69(3):508-515.
52. Khatami F, Larijani B, Heshmat R, et al (2017). Meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer. PLoS One, 12(9):e0184892.
53. Liu D, Hu S, Hou P, Jiang D, Condouris S, Xing M (2007). Suppression of BRAF/MEK/MAP kinase pathway restores expression of iodide-metabolizing genes in thyroid cells expressing the V600E BRAF mutant. Clin Cancer Res, 13(4):1341-9.
54. Joung KH, Shong M (2012). Epigenetic regulation of RUNX3 in thyroid carcinoma. Korean J Intern Med, 27(4):391-3.
55. Ko HJ, Kim BY, Jung CH, et al (2012). DNA Methylation of RUNX3 in Papillary Thyroid Cancer. Korean J Intern Med, 27(4):407-10.
56. Botezatu A, Iancu IV, Plesa A, et al (2019). Methylation of tumour suppressor genes associated with thyroid cancer. Cancer Biomark, 25(1):53-65.
57. Chuang LS, Ito Y (2010). RUNX3 is multifunctional in carcinogenesis of multiple solid tumors. Oncogene, 29(18):2605-15.
58. Chen F, Liu X, Bai J, Pei D, Zheng J (2016). The emerging role of RUNX3 in cancer metastasis (Review). Oncol Rep, 35(3):1227-36.
59. Hou P, Ji M, Xing M (2008). Association of PTEN gene methylation with genetic alterations in the phosphatidylinositol 3-kinase/AKT signaling pathway in thyroid tumors. Cancer, 113(9):2440-7.
60. Lu YM, Cheng F, Teng LS (2016). The association between phosphatase and tensin homolog hypermethylation and patients with breast cancer, a meta-analysis and literature review. Sci Re, 6:32723.
61. Georgescu MM (2010). PTEN Tumor Suppressor Network in PI3K-Akt Pathway Control. Genes & cancer, 1(12):1170-7.
62. Beg S, Siraj AK, Jehan Z, et al (2015). PTEN loss is associated with follicular variant of Middle Eastern papillary thyroid carcinoma. Br J Cancer, 112(12):1938-43.
63. Alvarez-Nuñez F, Bussaglia E, Mauricio D, et al (2006). PTEN promoter methylation in sporadic thyroid carcinomas. Thyroid, 16(1):17-23.
2. Smith JA, Fan CY, Zou C, Bodenner D, Kokoska MS (2007). Methylation status of genes in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg, 133(10):1006-11.
3. Stephen JK, Chitale D, Narra V, Chen KM, Sawhney R, Worsham MJ (2011). DNA methylation in thyroid tumorigenesis. Cancers (Basel), 3(2):1732-43.
4. Hedayati M, Nozhat Z, Hannani M (2016). Can the Serum Level of Myostatin be Considered as an Informative Factor for Cachexia Prevention in Patients with Medullary Thyroid Cancer? Asian Pac J Cancer Prev, 17(S3):119-23.
5. Qiang W, Zhao Y, Yang Q, et al (2014). ZIC1 is a putative tumor suppressor in thyroid cancer by modulating major signaling pathways and transcription factor FOXO3a. J Clin Endocrinol Metab, 99(7):E1163-72.
6. Stephen JK, Chen KM, Merritt J, Chitale D, Divine G, Worsham MJ (2018). Methylation markers differentiate thyroid cancer from benign nodules. J Endocrinol Invest, 41(2):163-70.
7. Hu S, Liu D, Tufano RP, et al (2006). Association of aberrant methylation of tumor suppressor genes with tumor aggressiveness and BRAF mutation in papillary thyroid cancer. Int J Cancer, 119(10):2322-9.
8. Xing M (2007). Gene methylation in thyroid tumorigenesis. Endocrinology, 148(3):948-53.
9. Lal G, Padmanabha L, Smith BJ, et al (2006). RIZ1 is epigenetically inactivated by promoter hypermethylation in thyroid carcinoma. Cancer, 107(12):2752-9.
10. Schagdarsurengin U, Gimm O, Dralle H, Hoang-Vu C, Dammann R (2006). CpG island methylation of tumor-related promoters occurs preferentially in undifferentiated carcinoma. Thyroid, 16(7):633-42.
11. Kanehisa M, Sato Y, Furumichi M, Morishima K, Tanabe M (2019). New approach for understanding genome variations in KEGG. Nucleic Acids Res, 47(D1):D590-d5.
12. Nikitin A, Egorov S, Daraselia N, Mazo I (2003). Pathway studio--the analysis and navigation of molecular networks. Bioinformatics, 19(16):2155-7.
13. Jiang JL, Tian GL, Chen SJ, Xu LI, Wang HQ (2015). Promoter methylation of p16 and RASSF1A genes may contribute to the risk of papillary thyroid cancer: A meta-analysis. Exp Ther Med, 10(4):1549-55.
14. Wang P, Pei R, Lu Z, Rao X, Liu B (2013). Methylation of p16 CpG islands correlated with metastasis and aggressiveness in papillary thyroid carcinoma. J Chin Med Assoc, 76(3):135-9.
15. Ben-Ari Fuchs S, Lieder I, Stelzer G, et al (2016). GeneAnalytics: An Integrative Gene Set Analysis Tool for Next Generation Sequencing, RNAseq and Microarray Data. Omics, 20(3):139-51.
16. Kamb A, Gruis NA, Weaver-Feldhaus J, et al (1994). A cell cycle regulator potentially involved in genesis of many tumor types. Science, 264(5157):436-40.
17. Elisei R, Shiohara M, Koeffler HP, Fagin JA (1998). Genetic and epigenetic alterations of the cyclin-dependent kinase inhibitors p15INK4b and p16INK4a in human thyroid carcinoma cell lines and primary thyroid carcinomas. Cancer, 83(10):2185-93.
18. Boltze C, Zack S, Quednow C, Bettge S, Roessner A, Schneider-Stock R (2003). Hypermethylation of the CDKN2/p16INK4A promotor in thyroid carcinogenesis. Pathol Res Pract, 199(6):399-404.
19. Lam AK, Lo CY, Leung P, Lang BH, Chan WF, Luk JM (2007). Clinicopathological roles of alterations of tumor suppressor gene p16 in papillary thyroid carcinoma. Ann Surg Oncol, 14(5):1772-9.
20. Mohammadi-asl J, Larijani B, Khorgami Z, et al (2011). Qualitative and quantitative promoter hypermethylation patterns of the P16, TSHR, RASSF1A and RARβ2 genes in papillary thyroid carcinoma. Med Oncol, 28(4):1123-8.
21. Wu W, Yang SF, Liu FF, Zhang JH (2015). Association between p16 Promoter Methylation and Thyroid Cancer Risk: A Meta-analysis. Asian Pac J Cancer Prev, 16(16):7111-5.
22. Donninger H, Vos MD, Clark GJ (2007). The RASSF1A tumor suppressor. J Cell Sci, 120(Pt 18):3163-72.
23. Xing M, Cohen Y, Mambo E, et al (2004). Early occurrence of RASSF1A hypermethylation and its mutual exclusion with BRAF mutation in thyroid tumorigenesis. Cancer Res, 64(5):1664-8.
24. Schagdarsurengin U, Gimm O, Hoang-Vu C, Dralle H, Pfeifer GP, Dammann R (2002). Frequent epigenetic silencing of the CpG island promoter of RASSF1A in thyroid carcinoma. Cancer Res, 62(13):3698-701.
25. Khatami F, Larijani B, Heshmat R, Nasiri S, Haddadi-Aghdam M, Teimoori-Toolabi L (2020). Hypermethylated RASSF1 and SLC5A8 promoters alongside BRAF(V600E) mutation as biomarkers for papillary thyroid carcinoma, J Cell Physiol, 235(10):6954-6968.
26. Hoque MO, Rosenbaum E, Westra WH, et al (2005). Quantitative assessment of promoter methylation profiles in thyroid neoplasms. J Clin Endocrinol Metab, 90(7):4011-8.
27. Shou F, Xu F, Li G, et al (2017). RASSF1A promoter methylation is associated with increased risk of thyroid cancer: a meta-analysis. Onco Targets Ther, 10:247-57.
28. Saavedra HI, Knauf JA, Shirokawa JM, et al (2000). The RAS oncogene induces genomic instability in thyroid PCCL3 cells via the MAPK pathway. Oncogene, 19(34):3948-54.
29. Schagdarsurengin U, Richter AM, Wohler C, Dammann RH (2009). Frequent epigenetic inactivation of RASSF10 in thyroid cancer. Epigenetics, 4(8):571-6.
30. Schagdarsurengin U, Richter AM, Hornung J, Lange C, Steinmann K, Dammann RH (2010). Frequent epigenetic inactivation of RASSF2 in thyroid cancer and functional consequences. Mol Cancer, 9:264.
31. Ganapathy V, Gopal E, Miyauchi S, Prasad PD (2005). Biological functions of SLC5A8, a candidate tumour suppressor. Biochem Soc Trans, 33(Pt 1):237-40.
32. Li H, Myeroff L, Smiraglia D, et al (003). SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc Natl Acad Sci U S A, 100(14):8412-7.
33. Park JY, Kim D, Yang M, et al (2013). Gene silencing of SLC5A8 identified by genome-wide methylation profiling in lung cancer. Lung Cancer, 79(3):198-204.
34. Babu E, Ramachandran S, Coothan Kandaswamy V, et al (2011). Role of SLC5A8, a plasma membrane transporter and a tumor suppressor, in the antitumor activity of dichloroacetate. Oncogene, 30(38):4026-37.
35. Kiseljak-Vassiliades K, Xing M (2011). Association of Cigarette Smoking with Aberrant Methylation of the Tumor Suppressor Gene RARbeta2 in Papillary Thyroid Cancer. Front Endocrinol (Lausanne), 2:99.
36. Zane M, Agostini M, Enzo MV, et al (2013). Circulating cell-free DNA, SLC5A8 and SLC26A4 hypermethylation, BRAF(V600E): A non-invasive tool panel for early detection of thyroid cancer. Biomed Pharmacother, 67(8):723-30.
37. Brait M, Loyo M, Rosenbaum E, et al (2012). Correlation between BRAF mutation and promoter methylation of TIMP3, RARbeta2 and RASSF1A in thyroid cancer. Epigenetics, 7(7):710-9.
38. Connolly RM, Nguyen NK, Sukumar S (2013). Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment. Clin Cancer Res, 19(7):1651-9.
39. Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K (2017). KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res, 45(D1):D353-d61.
40. Qi JH, Ebrahem Q, Moore N, et al (2003). A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med, 9(4):407-15.
41. Schneider-Stock R, Roessner A, Ullrich O (2005). DAP-kinase--protector or enemy in apoptotic cell death. Int J Biochem Cell Biol, 37(9):1763-7.
42. Brueckl WM, Grombach J, Wein A, et al (2005). Alterations in the tissue inhibitor of metalloproteinase-3 (TIMP-3) are found frequently in human colorectal tumours displaying either microsatellite stability (MSS) or instability (MSI). Cancer Lett, 223(1):137-42.
43. Darnton SJ, Hardie LJ, Muc RS, Wild CP, Casson AG (2005). Tissue inhibitor of metalloproteinase-3 (TIMP-3) gene is methylated in the development of esophageal adenocarcinoma: loss of expression correlates with poor prognosis. Int J Cancer, 115(3):351-8.
44. van der Velden PA, Zuidervaart W, Hurks MH, et al (2003). Expression profiling reveals that methylation of TIMP3 is involved in uveal melanoma development. Int J Cancer, 106(4):472-9.
45. Slenter DN, Kutmon M, Hanspers K, et al (2018). WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research. Nucleic Acids Res, 46(D1):D661-d7.
46. Maitland ML, Lou XJ, Ramirez J, et al (2010). Vascular endothelial growth factor pathway. Pharmacogenet Genomics, 20(5):346-9.
47. Whirl-Carrillo M, McDonagh EM, Hebert JM, et al (2012). Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther, 92(4):414-7.
48. Szkudlinski MW, Fremont V, Ronin C, Weintraub BD (2002). Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships. Physiol Reviews, 82(2):473-502.
49. Khan MS, Pandith AA, Masoodi SR, Wani KA, Ul Hussain M, Mudassar S (2014). Epigenetic silencing of TSHR gene in thyroid cancer patients in relation to their BRAF V600E mutation status. Endocrine, 47(2):449-55.
50. Kartal K, Onder S, Kosemehmetoglu K, Kilickap S, Tezel YG, Kaynaroglu V (2015). Methylation status of TSHr in well-differentiated thyroid cancer by using cytologic material. BMC Cancer, 15:824.
51. Qu M, Wan S, Ren B, Wu H, Liu L, Shen H (2020). Association between TSHR gene methylation and papillary thyroid cancer: a meta-analysis. Endocrine, 69(3):508-515.
52. Khatami F, Larijani B, Heshmat R, et al (2017). Meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer. PLoS One, 12(9):e0184892.
53. Liu D, Hu S, Hou P, Jiang D, Condouris S, Xing M (2007). Suppression of BRAF/MEK/MAP kinase pathway restores expression of iodide-metabolizing genes in thyroid cells expressing the V600E BRAF mutant. Clin Cancer Res, 13(4):1341-9.
54. Joung KH, Shong M (2012). Epigenetic regulation of RUNX3 in thyroid carcinoma. Korean J Intern Med, 27(4):391-3.
55. Ko HJ, Kim BY, Jung CH, et al (2012). DNA Methylation of RUNX3 in Papillary Thyroid Cancer. Korean J Intern Med, 27(4):407-10.
56. Botezatu A, Iancu IV, Plesa A, et al (2019). Methylation of tumour suppressor genes associated with thyroid cancer. Cancer Biomark, 25(1):53-65.
57. Chuang LS, Ito Y (2010). RUNX3 is multifunctional in carcinogenesis of multiple solid tumors. Oncogene, 29(18):2605-15.
58. Chen F, Liu X, Bai J, Pei D, Zheng J (2016). The emerging role of RUNX3 in cancer metastasis (Review). Oncol Rep, 35(3):1227-36.
59. Hou P, Ji M, Xing M (2008). Association of PTEN gene methylation with genetic alterations in the phosphatidylinositol 3-kinase/AKT signaling pathway in thyroid tumors. Cancer, 113(9):2440-7.
60. Lu YM, Cheng F, Teng LS (2016). The association between phosphatase and tensin homolog hypermethylation and patients with breast cancer, a meta-analysis and literature review. Sci Re, 6:32723.
61. Georgescu MM (2010). PTEN Tumor Suppressor Network in PI3K-Akt Pathway Control. Genes & cancer, 1(12):1170-7.
62. Beg S, Siraj AK, Jehan Z, et al (2015). PTEN loss is associated with follicular variant of Middle Eastern papillary thyroid carcinoma. Br J Cancer, 112(12):1938-43.
63. Alvarez-Nuñez F, Bussaglia E, Mauricio D, et al (2006). PTEN promoter methylation in sporadic thyroid carcinomas. Thyroid, 16(1):17-23.
| Files | ||
| Issue | Vol 50 No 12 (2021) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v50i12.7928 | |
| Keywords | ||
| DNA methylation Tumor suppressor gene Epigenetic Thyroid cancer Neoplasm | ||
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How to Cite
1.
Sheikkholeslami S, Zarif -Yeganeh M, Farashi S, Azizi F, Kheradmand Kia S, Teimoori-Toolabi L, Hedayati M. Promoter Methylation of Tumor Suppressors in Thyroid Carcinoma: A Systematic Review. Iran J Public Health. 2021;50(12):2461-2472.
