EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine

Abstract Small intestinal neuroendocrine tumors (SI-NETs) are slow-growing tumors that seem genetically quite stable without highly recurrent mutations, but are epigenetically dysregulated. In contrast to the undetectable expression of the enhancer of zeste homolog 2 (EZH2) histone methyltransferase...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Elham Barazeghi, Per Hellman, Olov Norlén, Gunnar Westin, Peter Stålberg
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
R
Q
Acceso en línea:https://doaj.org/article/d351b9e2cae3458c9b1d12c37c08e7b8
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:d351b9e2cae3458c9b1d12c37c08e7b8
record_format dspace
spelling oai:doaj.org-article:d351b9e2cae3458c9b1d12c37c08e7b82021-11-28T12:20:05ZEZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine10.1038/s41598-021-02181-72045-2322https://doaj.org/article/d351b9e2cae3458c9b1d12c37c08e7b82021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02181-7https://doaj.org/toc/2045-2322Abstract Small intestinal neuroendocrine tumors (SI-NETs) are slow-growing tumors that seem genetically quite stable without highly recurrent mutations, but are epigenetically dysregulated. In contrast to the undetectable expression of the enhancer of zeste homolog 2 (EZH2) histone methyltransferase in the enterochromaffin cells of the small intestine, we found high and differential expression of EZH2 in primary SI-NETs and corresponding metastases. Silencing EZH2 in the SI-NET cell line CNDT2.5 reduced cell proliferation and induced apoptosis. Furthermore, EZH2 knockout inhibited tumor progression in a CNDT2.5 SI-NET xenograft mouse model, and treatment of SI-NET cell lines CNDT2.5 and GOT1 with the EZH2-specific inhibitor CPI-1205 decreased cell viability and promoted apoptosis. Moreover, CPI-1205 treatment reduced migration capacity of CNDT2.5 cells. The EZH2 inhibitor GSK126 also repressed proliferation of CNDT2.5 cells. Recently, metformin has received wide attention as a therapeutic option in diverse cancers. In CNDT2.5 and GOT1 cells, metformin suppressed EZH2 expression, and inhibited cell proliferation. Exposure of GOT1 three-dimensional cell spheroids to CPI-1205 or metformin arrested cell proliferation and decreased spheroid size. These novel findings support a possible role of EZH2 as a candidate oncogene in SI-NETs, and suggest that CPI-1205 and metformin should be further evaluated as therapeutic options for patients with SI-NETs.Elham BarazeghiPer HellmanOlov NorlénGunnar WestinPeter StålbergNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Elham Barazeghi
Per Hellman
Olov Norlén
Gunnar Westin
Peter Stålberg
EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine
description Abstract Small intestinal neuroendocrine tumors (SI-NETs) are slow-growing tumors that seem genetically quite stable without highly recurrent mutations, but are epigenetically dysregulated. In contrast to the undetectable expression of the enhancer of zeste homolog 2 (EZH2) histone methyltransferase in the enterochromaffin cells of the small intestine, we found high and differential expression of EZH2 in primary SI-NETs and corresponding metastases. Silencing EZH2 in the SI-NET cell line CNDT2.5 reduced cell proliferation and induced apoptosis. Furthermore, EZH2 knockout inhibited tumor progression in a CNDT2.5 SI-NET xenograft mouse model, and treatment of SI-NET cell lines CNDT2.5 and GOT1 with the EZH2-specific inhibitor CPI-1205 decreased cell viability and promoted apoptosis. Moreover, CPI-1205 treatment reduced migration capacity of CNDT2.5 cells. The EZH2 inhibitor GSK126 also repressed proliferation of CNDT2.5 cells. Recently, metformin has received wide attention as a therapeutic option in diverse cancers. In CNDT2.5 and GOT1 cells, metformin suppressed EZH2 expression, and inhibited cell proliferation. Exposure of GOT1 three-dimensional cell spheroids to CPI-1205 or metformin arrested cell proliferation and decreased spheroid size. These novel findings support a possible role of EZH2 as a candidate oncogene in SI-NETs, and suggest that CPI-1205 and metformin should be further evaluated as therapeutic options for patients with SI-NETs.
format article
author Elham Barazeghi
Per Hellman
Olov Norlén
Gunnar Westin
Peter Stålberg
author_facet Elham Barazeghi
Per Hellman
Olov Norlén
Gunnar Westin
Peter Stålberg
author_sort Elham Barazeghi
title EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine
title_short EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine
title_full EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine
title_fullStr EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine
title_full_unstemmed EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine
title_sort ezh2 presents a therapeutic target for neuroendocrine tumors of the small intestine
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/d351b9e2cae3458c9b1d12c37c08e7b8
work_keys_str_mv AT elhambarazeghi ezh2presentsatherapeutictargetforneuroendocrinetumorsofthesmallintestine
AT perhellman ezh2presentsatherapeutictargetforneuroendocrinetumorsofthesmallintestine
AT olovnorlen ezh2presentsatherapeutictargetforneuroendocrinetumorsofthesmallintestine
AT gunnarwestin ezh2presentsatherapeutictargetforneuroendocrinetumorsofthesmallintestine
AT peterstalberg ezh2presentsatherapeutictargetforneuroendocrinetumorsofthesmallintestine
_version_ 1718408046033502208