Cover image of the article: Vitamin D and Regulation of Histone Methyltransferase EZH2 in Anaplastic Thyroid Carcinoma, From Mechanism to Therapeutic Potential. A Review Article

Image Credit:Koomesh

Vitamin D and Regulation of Histone Methyltransferase EZH2 in Anaplastic Thyroid Carcinoma, From Mechanism to Therapeutic Potential. A Review Article

Authors

Shamsedin Salim AlaghehbandShamsedin Salim Alaghehband ORCID1, Flora ForouzeshFlora Forouzesh ORCID1, Mehdi HedayatiMehdi Hedayati ORCID2,*
1Department of Genetics, TeMS.C., Islamic Azad University, Tehran, Iran
2Cellular and Molecular Endocrine Research center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
*Corresponding Author: Cellular and Molecular Endocrine Research center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran Email: hedayati47@gmail.com

Koomesh:Vol. 28, issue 2; e157927
Published online:Aug 03, 2026
Article type:Review Article
How to Cite:Salim Alaghehband S, Forouzesh F, Hedayati M. Vitamin D and Regulation of Histone Methyltransferase EZH2 in Anaplastic Thyroid Carcinoma, From Mechanism to Therapeutic Potential. A Review Article. Koomesh. 2026;28(2):e157927. doi: https://doi.org/10.69107/koomesh-157927

References

  • 1.
    Cocolos A-M, Poiana C. Differentiated Thyroid Cancer Genetic Mechanisms - Focus on Vitamin D Receptor and Methylenetetrahydrofolate Reductase Gene Polymorphisms. Mod Med. 2022;29(1):7–13. https://doi.org/10.31689/rmm.2021.29.1.7.
  • 2.
    Saini S, Tulla K, Maker AV, Burman KD, Prabhakar BS. Therapeutic advances in anaplastic thyroid cancer: a current perspective. Mol Cancer. 2018;17(1):154. [PubMed ID:30352606]. [PubMed Central ID:PMC6198524]. https://doi.org/10.1186/s12943-018-0903-0.
  • 3.
    Prete A, Borges de Souza P, Censi S, Muzza M, Nucci N, Sponziello M. Update on Fundamental Mechanisms of Thyroid Cancer. Front Endocrinol (Lausanne). 2020;11:102. [PubMed ID:32231639]. [PubMed Central ID:PMC7082927]. https://doi.org/10.3389/fendo.2020.00102.
  • 4.
    Hall JE, Hall ME. Guyton and Hall Textbook of Medical Physiology. Philadelphia, Pennsylvania: Elsevier; 2021. p. 549-558.
  • 5.
    Norasti F, Yeganeh MZ, Sheikholeslami S, Rad LH, Ghadaksaz HG, Hedayati M. [Plasma levels of omentin in patients with medullary thyroid carcinoma]. Koomesh. 2019;21(1):e15304. Persian.
  • 6.
    Sasanakietkul T, Murtha TD, Javid M, Korah R, Carling T. Epigenetic modifications in poorly differentiated and anaplastic thyroid cancer. Mol Cell Endocrinol. 2018;469:23–37. [PubMed ID:28552796]. https://doi.org/10.1016/j.mce.2017.05.022.
  • 7.
    Smith N, Nucera C. Personalized therapy in patients with anaplastic thyroid cancer: targeting genetic and epigenetic alterations. J Clin Endocrinol Metab. 2015;100(1):35–42. [PubMed ID:25347569]. [PubMed Central ID:PMC4283016]. https://doi.org/10.1210/jc.2014-2803.
  • 8.
    Shakiba E, Movahedi M, Majd A, Hedayati M. [Genetic and epigenetic alteration in thyroid cancer: review article]. Tehran Univ Med J. 2018;75(12):849–59. Persian.
  • 9.
    Ivor JB, Griggs RC, Wing EJ, Fitz G. Cecil Essentials of Medicine. Amsterdam, Netherlands: Elsevier; 2016. p. 633-641.
  • 10.
    Yang J, Barletta JA. Anaplastic thyroid carcinoma. Semin Diagn Pathol. 2020;37(5):248–56. [PubMed ID:32624319]. https://doi.org/10.1053/j.semdp.2020.06.005.
  • 11.
    Bhattacharya S, Mahato RK, Singh S, Bhatti GK, Mastana SS, Bhatti JS. Advances and challenges in thyroid cancer: The interplay of genetic modulators, targeted therapies, and AI-driven approaches. Life Sci. 2023;332:122110. [PubMed ID:37734434]. https://doi.org/10.1016/j.lfs.2023.122110.
  • 12.
    Yuan J, Guo Y. Targeted Therapy for Anaplastic Thyroid Carcinoma: Advances and Management. Cancers (Basel). 2022;15(1). [PubMed ID:36612173]. [PubMed Central ID:PMC9818071]. https://doi.org/10.3390/cancers15010179.
  • 13.
    Lyu Z, Zhang Y, Sheng C, Huang Y, Zhang Q, Chen K. Global burden of thyroid cancer in 2022: Incidence and mortality estimates from GLOBOCAN. Chin Med J (Engl). 2024;137(21):2567–76. [PubMed ID:39261986]. [PubMed Central ID:PMC11557048]. https://doi.org/10.1097/CM9.0000000000003284.
  • 14.
    Pejman Sani M, Mohseni S, Samimi H, Nasiri S, Fallahi B, Mohajeri-Tehrani M, et al. Continued rise in the incidence of thyroid cancer in Iran: true increase or overdiagnosis? J Diabetes Metab Disord. 2025;24(1):68. [PubMed ID:39980844]. [PubMed Central ID:PMC11836260]. https://doi.org/10.1007/s40200-025-01581-0.
  • 15.
    Azangou-Khyavy M, Saeedi Moghaddam S, Rezaei N, Esfahani Z, Rezaei N, Azadnajafabad S, et al. National, sub-national, and risk-attributed burden of thyroid cancer in Iran from 1990 to 2019. Sci Rep. 2022;12(1):13231. [PubMed ID:35918489]. [PubMed Central ID:PMC9346133]. https://doi.org/10.1038/s41598-022-17115-0.
  • 16.
    Lubitz CC, Sadow PM, Daniels GH, Wirth LJ. Progress in Treating Advanced Thyroid Cancers in the Era of Targeted Therapy. Thyroid. 2021;31(10):1451–62. [PubMed ID:33860688]. [PubMed Central ID:PMC8591086]. https://doi.org/10.1089/thy.2020.0962.
  • 17.
    Li Z, Zhang Y, Wang R, Zou K, Zou L. Genetic alterations in anaplastic thyroid carcinoma and targeted therapies (Review). Experimental Therapeutic Med. 2019;18(4):2369–77. https://doi.org/10.3892/etm.2019.7869.
  • 18.
    Rao SN, Smallridge RC. Anaplastic thyroid cancer: An update. Best Pract Res Clin Endocrinol Metab. 2023;37(1):101678. [PubMed ID:35668021]. https://doi.org/10.1016/j.beem.2022.101678.
  • 19.
    Evans LK, Chen H, Taki Labib M, Cronkite DA, Yu AC, Ashendouek M, et al. Improved Survival of Advanced-Stage Anaplastic Thyroid Cancer With Systemic Therapy. Laryngoscope. 2025;135(1):478–84. [PubMed ID:39162326]. [PubMed Central ID:PMC11635144]. https://doi.org/10.1002/lary.31712.
  • 20.
    Zhang L, Feng Q, Wang J, Tan Z, Li Q, Ge M. Molecular basis and targeted therapy in thyroid cancer: Progress and opportunities. Biochim Biophys Acta Rev Cancer. 2023;1878(4):188928. [PubMed ID:37257629]. https://doi.org/10.1016/j.bbcan.2023.188928.
  • 21.
    Salehian B, Liem SY, Mojazi Amiri H, Maghami E. Clinical Trials in Management of Anaplastic Thyroid Carcinoma; Progressions and Set Backs: A Systematic Review. Int J Endocrinol Metab. 2019;17(1):e67759. [PubMed ID:30881466]. [PubMed Central ID:PMC6408732]. https://doi.org/10.5812/ijem.67759.
  • 22.
    Zhang Y, Chen J, Liu H, Mi R, Huang R, Li X, et al. The role of histone methylase and demethylase in antitumor immunity: A new direction for immunotherapy. Front Immunol. 2022;13:1099892. [PubMed ID:36713412]. [PubMed Central ID:PMC9874864]. https://doi.org/10.3389/fimmu.2022.1099892.
  • 23.
    Trager MH, Sah B, Chen Z, Liu L. Control of Breast Cancer Pathogenesis by Histone Methylation and the Hairless Histone Demethylase. Endocrinology. 2021;162(8). [PubMed ID:33928351]. [PubMed Central ID:PMC8237996]. https://doi.org/10.1210/endocr/bqab088.
  • 24.
    Liao Q, Yang J, Ge S, Chai P, Fan J, Jia R. Novel insights into histone lysine methyltransferases in cancer therapy: From epigenetic regulation to selective drugs. J Pharm Anal. 2023;13(2):127–41. [PubMed ID:36908859]. [PubMed Central ID:PMC9999304]. https://doi.org/10.1016/j.jpha.2022.11.009.
  • 25.
    Babic Leko M, Juresko I, Rozic I, Pleic N, Gunjaca I, Zemunik T. Vitamin D and the Thyroid: A Critical Review of the Current Evidence. Int J Mol Sci. 2023;24(4). [PubMed ID:36835005]. [PubMed Central ID:PMC9964959]. https://doi.org/10.3390/ijms24043586.
  • 26.
    Masudo K, Suganuma N, Nakayama H, Oshima T, Rino Y, Iwasaki H. EZH2 Overexpression as a Useful Prognostic Marker for Aggressive Behaviour in Thyroid Cancer. In Vivo. 2018;32(1). https://doi.org/10.21873/invivo.11200.
  • 27.
    Duan R, Du W, Guo W. EZH2: a novel target for cancer treatment. J Hematol Oncol. 2020;13(1):104. [PubMed ID:32723346]. [PubMed Central ID:PMC7385862]. https://doi.org/10.1186/s13045-020-00937-8.
  • 28.
    Borbone E, Troncone G, Ferraro A, Jasencakova Z, Stojic L, Esposito F, et al. Enhancer of zeste homolog 2 overexpression has a role in the development of anaplastic thyroid carcinomas. J Clin Endocrinol Metab. 2011;96(4):1029–38. [PubMed ID:21289264]. https://doi.org/10.1210/jc.2010-1784.
  • 29.
    Yamaguchi H, Hung MC. Regulation and Role of EZH2 in Cancer. Cancer Res Treat. 2014;46(3):209–22. [PubMed ID:25038756]. [PubMed Central ID:PMC4132442]. https://doi.org/10.4143/crt.2014.46.3.209.
  • 30.
    Xu M, Xu C, Wang R, Tang Q, Zhou Q, Wu W, et al. Treating human cancer by targeting EZH2. Genes Dis. 2025;12(3):101313. [PubMed ID:40028035]. [PubMed Central ID:PMC11870178]. https://doi.org/10.1016/j.gendis.2024.101313.
  • 31.
    Volkel P, Dupret B, Le Bourhis X, Angrand PO. Diverse involvement of EZH2 in cancer epigenetics. Am J Transl Res. 2015;7(2):175–93. [PubMed ID:25901190]. [PubMed Central ID:PMC4399085].
  • 32.
    Sun S, Yu F, Zhang L, Zhou X. EZH2, an on-off valve in signal network of tumor cells. Cell Signal. 2016;28(5):481–7. [PubMed ID:26876615]. https://doi.org/10.1016/j.cellsig.2016.02.004.
  • 33.
    Nakayama H, Saito N, Kasajima R, Suganuma N, Rino Y, Masudo K, et al. Validation of EZH2 Inhibitor Efficiency in Anaplastic Thyroid Carcinoma Cell Lines. Anticancer Res. 2023;43(3):1073–7. [PubMed ID:36854530]. https://doi.org/10.21873/anticanres.16252.
  • 34.
    de Mello DC, Saito KC, Cristovao MM, Kimura ET, Fuziwara CS. Modulation of EZH2 Activity Induces an Antitumoral Effect and Cell Redifferentiation in Anaplastic Thyroid Cancer. Int J Mol Sci. 2023;24(9). [PubMed ID:37175580]. [PubMed Central ID:PMC10178714]. https://doi.org/10.3390/ijms24097872.
  • 35.
    Lachat C, Boyer-Guittaut M, Peixoto P, Hervouet E. Epigenetic Regulation of EMT (Epithelial to Mesenchymal Transition) and Tumor Aggressiveness: A View on Paradoxical Roles of KDM6B and EZH2. Epigenomes. 2018;3(1). [PubMed ID:34991274]. [PubMed Central ID:PMC8594212]. https://doi.org/10.3390/epigenomes3010001.
  • 36.
    Wen Y, Cai J, Hou Y, Huang Z, Wang Z. Role of EZH2 in cancer stem cells: from biological insight to a therapeutic target. Oncotarget. 2017;8(23):37974–90. [PubMed ID:28415635]. [PubMed Central ID:PMC5514966]. https://doi.org/10.18632/oncotarget.16467.
  • 37.
    Maciejewski A, Lacka K. Vitamin D-Related Genes and Thyroid Cancer-A Systematic Review. Int J Mol Sci. 2022;23(21). [PubMed ID:36362448]. [PubMed Central ID:PMC9658610]. https://doi.org/10.3390/ijms232113661.
  • 38.
    Suzuki S, Takenoshita S, Furukawa H, Tsuchiya A. Antineoplastic activity of 1,25(OH)2D3 and its analogue 22-oxacalcitriol against human anaplastic thyroid carcinoma cell lines in vitro. Int J Mol Med. 1999. https://doi.org/10.3892/ijmm.4.6.611.
  • 39.
    Henn M, Martin-Gorgojo V, Martin-Moreno JM. Vitamin D in Cancer Prevention: Gaps in Current Knowledge and Room for Hope. Nutrients. 2022;14(21). [PubMed ID:36364774]. [PubMed Central ID:PMC9657468]. https://doi.org/10.3390/nu14214512.
  • 40.
    Fetahu IS, Hobaus J, Kallay E. Vitamin D and the epigenome. Front Physiol. 2014;5:164. [PubMed ID:24808866]. [PubMed Central ID:PMC4010791]. https://doi.org/10.3389/fphys.2014.00164.
  • 41.
    Peng W, Wang K, Zheng R, Derwahl M. 1,25 dihydroxyvitamin D3 inhibits the proliferation of thyroid cancer stem-like cells via cell cycle arrest. Endocr Res. 2016;41(2):71–80. [PubMed ID:27030645]. https://doi.org/10.3109/07435800.2015.1037048.
  • 42.
    Fernandez-Barral A, Bustamante-Madrid P, Ferrer-Mayorga G, Barbachano A, Larriba MJ, Munoz A. Vitamin D Effects on Cell Differentiation and Stemness in Cancer. Cancers (Basel). 2020;12(9). [PubMed ID:32854355]. [PubMed Central ID:PMC7563562]. https://doi.org/10.3390/cancers12092413.
  • 43.
    Ng K, Ou FS, Zemla T, McCleary N, Kalyan A, Shusterman M, et al. LBA26 SOLARIS (Alliance A021703): A multicenter double-blind phase III randomized clinical trial (RCT) of vitamin D (VitD) combined with standard chemotherapy plus bevacizumab (bev) in patients (pts) with previously untreated metastatic colorectal cancer (mCRC). Ann Oncol. 2024;35. https://doi.org/10.1016/j.annonc.2024.08.2265.
  • 44.
    Omodei MS, Chimicoviaki J, Buttros DAB, Almeida-Filho BS, Carvalho-Pessoa CP, Carvalho-Pessoa E, et al. Vitamin D Supplementation Improves Pathological Complete Response in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy: A Randomized Clinical Trial. Nutr Cancer. 2025;77(6):648–57. [PubMed ID:40098326]. https://doi.org/10.1080/01635581.2025.2480854.
  • 45.
    Ozkurt E, Ordu C, Ozmen T, Ilgun AS, Soybir G, Celebi F, et al. Vitamin D Supplementation During Neoadjuvant Chemotherapy for Breast Cancer Improves Pathological Complete Response: A Prospective Randomized Clinical Trial. World J Surg. 2025;49(6):1396–405. [PubMed ID:40229998]. [PubMed Central ID:PMC12134193]. https://doi.org/10.1002/wjs.12587.
  • 46.
    Trujano-Camacho S, Pulido-Capiz A, Garcia-Gonzalez V, Lopez-Urrutia E, Perez-Plasencia C. Vitamin D as an Epigenetic Regulator: A Hypothetical Mechanism for Cancer Prevention via Inhibition of Oncogenic lncRNA HOTAIR. Int J Mol Sci. 2025;26(16). [PubMed ID:40869316]. [PubMed Central ID:PMC12386503]. https://doi.org/10.3390/ijms26167997.

Copyright

© 2026, Author(s). This open-access article is available under the Creative Commons Attribution 4.0 (CC BY 4.0) International License (https://creativecommons.org/licenses/by/4.0/), which allows for unrestricted use, distribution, and reproduction in any medium, provided that the original work is properly cited.

Similar Articles

31
Jan
2021
Anticancer Effects of Valproic Acid via Regulation of Epigenetic Mechanisms in Non-small-cell Lung Cancer A549 Cell Line

Anticancer Effects of Valproic Acid via Regulation of Epigenetic Mechanisms in Non-small-cell Lung Cancer A549 Cell Line

Hadi Kalantar,
Mohsen Rashidi,
Mojtaba Kalantar,
Mahmoud Tavallaei,
Sayed Mostafa Hosseini

Kalantar H, Rashidi M, Kalantar M, Tavallaei M, Hosseini SM. Anticancer Effects of Valproic Acid via Regulation of Epigenetic Mechanisms in Non-small-cell Lung Cancer A549 Cell Line. Iran J Pharm Res. 2021;20(1):e124473. doi: https://doi.org/10.22037/ijpr.2019.111945.13442

31
Jul
2021
Histone Deacetylase Inhibitors, Intrinsic and Extrinsic Apoptotic Pathways, and Epigenetic Alterations of Histone Deacetylases (HDACs) in Hepatocellular Carcinoma

Histone Deacetylase Inhibitors, Intrinsic and Extrinsic Apoptotic Pathways, and Epigenetic Alterations of Histone Deacetylases (HDACs) in Hepatocellular Carcinoma

Masumeh Sanaei,
Fraidoon Kavoosi

Sanaei M, Kavoosi F. Histone Deacetylase Inhibitors, Intrinsic and Extrinsic Apoptotic Pathways, and Epigenetic Alterations of Histone Deacetylases (HDACs) in Hepatocellular Carcinoma. Iran J Pharm Res. 2021;20(3):e124318. doi: https://doi.org/10.22037/ijpr.2021.115105.15197

22
Dec
2025
Epstein-Barr Virus and Outcomes of Minimally Invasive Thyroid Ablation: A Systematic Review and Meta-Analysis

Epstein-Barr Virus and Outcomes of Minimally Invasive Thyroid Ablation: A Systematic Review and Meta-Analysis

Xiaojie Liu,
Chao Yang,
Wanjing Hu

Liu X, Yang C, Hu W. Epstein-Barr Virus and Outcomes of Minimally Invasive Thyroid Ablation: A Systematic Review and Meta-Analysis. Jundishapur J Microbiol. 2026;19(1):e165493. doi: https://doi.org/10.5812/jjm-165493

17
Feb
2020
In Vitro and In Vivo Antitumor Activity of Vitamin D3 in Malignant Gliomas: A Systematic Review

In Vitro and In Vivo Antitumor Activity of Vitamin D3 in Malignant Gliomas: A Systematic Review

Melika Hajimohammadebrahim-Ketabforoush,
Zahra Vahdat Shariatpanahi,
Mohammadreza Shahmohammadi

Hajimohammadebrahim-Ketabforoush M, Vahdat Shariatpanahi Z, Shahmohammadi M. In Vitro and In Vivo Antitumor Activity of Vitamin D3 in Malignant Gliomas: A Systematic Review. Int J Cancer Manag. 2020;13(2):e94542. doi: https://doi.org/10.5812/ijcm.94542

14
Jun
2023
The Relationship Between Vitamin D Deficiency and Laryngeal Cancer: A Case-control Study in Mashhad, Iran

The Relationship Between Vitamin D Deficiency and Laryngeal Cancer: A Case-control Study in Mashhad, Iran

Ehsan Khadivi,
Negar Moghaddas,
Hamidreza Rasti Boroujeni,
Bashir Rasoulian,
Mohammadreza Afzalzadeh,
Maryam Emadzadeh
,et al.

Khadivi E, Moghaddas N, Rasti Boroujeni H, Rasoulian B, Afzalzadeh M, et al. The Relationship Between Vitamin D Deficiency and Laryngeal Cancer: A Case-control Study in Mashhad, Iran. Int J Cancer Manag. 2023;16(1):e135578. doi: https://doi.org/10.5812/ijcm-135578

More by these authors

Shamsedin Salim AlaghehbandPubMedScholar
Flora ForouzeshPubMedScholar
Mehdi HedayatiPubMedScholar
Share
Cited by
Metrics
Indexed in