Epigenetic Dysregulation of in Human Glioblastoma

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Jun 15

PMID 29899831

Citations 26

Authors

Maria G Garcia

Antonella Carella

Rocio G Urdinguio

Gustavo F Bayon

Virginia Lopez

Juan Ramon Tejedor

Marta I Sierra

Estela Garcia-Torano

Pablo Santamarina

Raul F Perez

Cristina Mangas

Aurora Astudillo

M Daniela Corte-Torres

Ines Saenz-de-Santa-Maria

Maria-Dolores Chiara

Agustin F Fernandez

Mario F Fraga

Affiliations

Soon will be listed here.

Abstract

Ten-eleven translocation (TET) enzymes are frequently deregulated in cancer, but the underlying molecular mechanisms are still poorly understood. Here we report that shows frequent epigenetic alterations in human glioblastoma including DNA hypermethylation and hypo-hydroxymethylation, as well as loss of histone acetylation. Ectopic overexpression of regulated neural differentiation in glioblastoma cell lines and impaired tumor growth. Our results suggest that epigenetic dysregulation of plays a role in human glioblastoma.

Citing Articles

The Role of DNMT Methyltransferases and TET Dioxygenases in the Maintenance of the DNA Methylation Level.

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Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review.

Shen Y, Thng D, Wong A, Toh T Exp Hematol Oncol. 2024; 13(1):40.

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Lower Levels of TET2 Gene Expression, with a Higher Level of TET2 Promoter Methylation in Patients with AML; Evidence for the Role of Aberrant Methylation in AML Pathogenesis.

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Identification and validation of 5-methylcytosine-associated genes in diffuse large B-cell lymphoma.

Xing C, Zhu S, Yan W, Zhu H, Huang Z, Zhao Y Heliyon. 2023; 9(11):e22209.

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The Role of Non-Coding RNAs in Epigenetic Dysregulation in Glioblastoma Development.

Isachesku E, Braicu C, Pirlog R, Kocijancic A, Busuioc C, Pruteanu L Int J Mol Sci. 2023; 24(22).

PMID: 38003512 PMC: 10671451. DOI: 10.3390/ijms242216320.

References

Hutton S, Pevny L . SOX2 expression levels distinguish between neural progenitor populations of the developing dorsal telencephalon. Dev Biol. 2011; 352(1):40-7. DOI: 10.1016/j.ydbio.2011.01.015. View

Sommer L, Shah N, Rao M, Anderson D . The cellular function of MASH1 in autonomic neurogenesis. Neuron. 1995; 15(6):1245-58. DOI: 10.1016/0896-6273(95)90005-5. View

Scourzic L, Mouly E, Bernard O . TET proteins and the control of cytosine demethylation in cancer. Genome Med. 2015; 7(1):9. PMC: 4308928. DOI: 10.1186/s13073-015-0134-6. View

Rasmussen K, Jia G, Johansen J, Pedersen M, Rapin N, Bagger F . Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis. Genes Dev. 2015; 29(9):910-22. PMC: 4421980. DOI: 10.1101/gad.260174.115. View

Orr B, Haffner M, Nelson W, Yegnasubramanian S, Eberhart C . Decreased 5-hydroxymethylcytosine is associated with neural progenitor phenotype in normal brain and shorter survival in malignant glioma. PLoS One. 2012; 7(7):e41036. PMC: 3400598. DOI: 10.1371/journal.pone.0041036. View

Makeyev E, Zhang J, Carrasco M, Maniatis T . The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell. 2007; 27(3):435-48. PMC: 3139456. DOI: 10.1016/j.molcel.2007.07.015. View

Pan F, Weeks O, Yang F, Xu M . The TET2 interactors and their links to hematological malignancies. IUBMB Life. 2015; 67(6):438-45. PMC: 4765929. DOI: 10.1002/iub.1389. View

Santiago M, Antunes C, Guedes M, Sousa N, Marques C . TET enzymes and DNA hydroxymethylation in neural development and function - how critical are they?. Genomics. 2014; 104(5):334-40. DOI: 10.1016/j.ygeno.2014.08.018. View

Lopez V, Fernandez A, Fraga M . The role of 5-hydroxymethylcytosine in development, aging and age-related diseases. Ageing Res Rev. 2017; 37:28-38. DOI: 10.1016/j.arr.2017.05.002. View

10.

Taylor G, Eskeland R, Hekimoglu-Balkan B, Pradeepa M, Bickmore W . H4K16 acetylation marks active genes and enhancers of embryonic stem cells, but does not alter chromatin compaction. Genome Res. 2013; 23(12):2053-65. PMC: 3847775. DOI: 10.1101/gr.155028.113. View

11.

Dawlaty M, Breiling A, Le T, Raddatz G, Barrasa M, Cheng A . Combined deficiency of Tet1 and Tet2 causes epigenetic abnormalities but is compatible with postnatal development. Dev Cell. 2013; 24(3):310-23. PMC: 3574201. DOI: 10.1016/j.devcel.2012.12.015. View

12.

Yi S, Jo A, Park C, Koh H, Park R, Suh-Kim H . Mash1 and neurogenin 2 enhance survival and differentiation of neural precursor cells after transplantation to rat brains via distinct modes of action. Mol Ther. 2008; 16(11):1873-82. DOI: 10.1038/mt.2008.189. View

13.

Maksimovic J, Gordon L, Oshlack A . SWAN: Subset-quantile within array normalization for illumina infinium HumanMethylation450 BeadChips. Genome Biol. 2012; 13(6):R44. PMC: 3446316. DOI: 10.1186/gb-2012-13-6-r44. View

14.

Wang Y, Xiao M, Chen X, Chen L, Xu Y, Lv L . WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation. Mol Cell. 2015; 57(4):662-673. PMC: 4336627. DOI: 10.1016/j.molcel.2014.12.023. View

15.

Li X, Yao B, Chen L, Kang Y, Li Y, Cheng Y . Ten-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis. Nat Commun. 2017; 8:15903. PMC: 5493768. DOI: 10.1038/ncomms15903. View

16.

Langemeijer S, Kuiper R, Berends M, Knops R, Aslanyan M, Massop M . Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet. 2009; 41(7):838-42. DOI: 10.1038/ng.391. View

17.

Bernard O, Delhommeau F, Fontenay M, Vainchenker W . [Mutations in TET2 in myeloid cancers]. Med Sci (Paris). 2009; 25(10):785-8. DOI: 10.1051/medsci/20092510785. View

18.

Qiao Y, Wang X, Wang R, Li Y, Yu F, Yang X . AF9 promotes hESC neural differentiation through recruiting TET2 to neurodevelopmental gene loci for methylcytosine hydroxylation. Cell Discov. 2016; 1:15017. PMC: 4860857. DOI: 10.1038/celldisc.2015.17. View

19.

Zhang W, Shao Z, Fu R, Wang H, Li L, Wang J . TET2 Expression in Bone Marrow Mononuclear Cells of Patients with Myelodysplastic Syndromes and Its Clinical Significances. Cancer Biol Med. 2013; 9(1):34-7. PMC: 3643638. DOI: 10.3969/j.issn.2095-3941.2012.01.006. View

20.

Barazeghi E, Gill A, Sidhu S, Norlen O, Dina R, Palazzo F . A role for in parathyroid carcinoma. Endocr Relat Cancer. 2017; 24(7):329-338. DOI: 10.1530/ERC-17-0009. View