Hypomethylation of CNTFRα is associated with proliferation and poor prognosis in lower grade gliomas

Abstract Ciliary neurotrophic factor receptor α subunit (CNTFRα) and CNTF play important roles in neuron survival, glial differentiation and brain tumor growth. However, the molecular mechanisms of CNTFRα regulation and its clinical significance in glioma remain largely unknown. Here, we found CNTFR...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kun Fan, Xiaowen Wang, Jingwen Zhang, Romela Irene Ramos, Haibo Zhang, Chunjie Li, Dan Ye, Jiansheng Kang, Diego M. Marzese, Dave S. B. Hoon, Wei Hua
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4caaa1c465b54501b3314f2f0aad6ec5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4caaa1c465b54501b3314f2f0aad6ec5
record_format	dspace
spelling	oai:doaj.org-article:4caaa1c465b54501b3314f2f0aad6ec52021-12-02T12:32:52ZHypomethylation of CNTFRα is associated with proliferation and poor prognosis in lower grade gliomas10.1038/s41598-017-07124-92045-2322https://doaj.org/article/4caaa1c465b54501b3314f2f0aad6ec52017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07124-9https://doaj.org/toc/2045-2322Abstract Ciliary neurotrophic factor receptor α subunit (CNTFRα) and CNTF play important roles in neuron survival, glial differentiation and brain tumor growth. However, the molecular mechanisms of CNTFRα regulation and its clinical significance in glioma remain largely unknown. Here, we found CNTFRα was overexpressed in lower grade gliomas (LGG) compared with glioblastoma (GBM) and normal brain specimens in TCGA datasets and in an independent cohort. Bioinformatics analysis revealed a CpG shore of the CNTFRα gene regulated its mRNA expression in TCGA datasets. This observation was further validated with clinical specimens and functionally verified using demethylating agents. Additionally, we observed that independent of IDH mutation status, methylation of CNTFRα was significantly correlated with down-regulated CNTFRα gene expression and longer LGG patient survival. Interestingly, combination of CNTFRα methylation and IDH mutation significantly (p < 0.05) improved the prognostic prediction in LGG patients. Furthermore, the role of CNTFRα in glioma proliferation and apoptosis through the PI3K/AKT pathways was demonstrated by supplementation with exogenous CNTF in vitro and siRNA knockdown in vivo. Our study demonstrated that hypomethylation leading to CNTFRα up-regulation, together with autocrine expression of CNTF, was involved in glioma growth regulation. Importantly, DNA methylation of CNTFRα might serve as a potential epigenetic theranostic target for LGG patients.Kun FanXiaowen WangJingwen ZhangRomela Irene RamosHaibo ZhangChunjie LiDan YeJiansheng KangDiego M. MarzeseDave S. B. HoonWei HuaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kun Fan Xiaowen Wang Jingwen Zhang Romela Irene Ramos Haibo Zhang Chunjie Li Dan Ye Jiansheng Kang Diego M. Marzese Dave S. B. Hoon Wei Hua Hypomethylation of CNTFRα is associated with proliferation and poor prognosis in lower grade gliomas
description	Abstract Ciliary neurotrophic factor receptor α subunit (CNTFRα) and CNTF play important roles in neuron survival, glial differentiation and brain tumor growth. However, the molecular mechanisms of CNTFRα regulation and its clinical significance in glioma remain largely unknown. Here, we found CNTFRα was overexpressed in lower grade gliomas (LGG) compared with glioblastoma (GBM) and normal brain specimens in TCGA datasets and in an independent cohort. Bioinformatics analysis revealed a CpG shore of the CNTFRα gene regulated its mRNA expression in TCGA datasets. This observation was further validated with clinical specimens and functionally verified using demethylating agents. Additionally, we observed that independent of IDH mutation status, methylation of CNTFRα was significantly correlated with down-regulated CNTFRα gene expression and longer LGG patient survival. Interestingly, combination of CNTFRα methylation and IDH mutation significantly (p < 0.05) improved the prognostic prediction in LGG patients. Furthermore, the role of CNTFRα in glioma proliferation and apoptosis through the PI3K/AKT pathways was demonstrated by supplementation with exogenous CNTF in vitro and siRNA knockdown in vivo. Our study demonstrated that hypomethylation leading to CNTFRα up-regulation, together with autocrine expression of CNTF, was involved in glioma growth regulation. Importantly, DNA methylation of CNTFRα might serve as a potential epigenetic theranostic target for LGG patients.
format	article
author	Kun Fan Xiaowen Wang Jingwen Zhang Romela Irene Ramos Haibo Zhang Chunjie Li Dan Ye Jiansheng Kang Diego M. Marzese Dave S. B. Hoon Wei Hua
author_facet	Kun Fan Xiaowen Wang Jingwen Zhang Romela Irene Ramos Haibo Zhang Chunjie Li Dan Ye Jiansheng Kang Diego M. Marzese Dave S. B. Hoon Wei Hua
author_sort	Kun Fan
title	Hypomethylation of CNTFRα is associated with proliferation and poor prognosis in lower grade gliomas
title_short	Hypomethylation of CNTFRα is associated with proliferation and poor prognosis in lower grade gliomas
title_full	Hypomethylation of CNTFRα is associated with proliferation and poor prognosis in lower grade gliomas
title_fullStr	Hypomethylation of CNTFRα is associated with proliferation and poor prognosis in lower grade gliomas
title_full_unstemmed	Hypomethylation of CNTFRα is associated with proliferation and poor prognosis in lower grade gliomas
title_sort	hypomethylation of cntfrα is associated with proliferation and poor prognosis in lower grade gliomas
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4caaa1c465b54501b3314f2f0aad6ec5
work_keys_str_mv	AT kunfan hypomethylationofcntfraisassociatedwithproliferationandpoorprognosisinlowergradegliomas AT xiaowenwang hypomethylationofcntfraisassociatedwithproliferationandpoorprognosisinlowergradegliomas AT jingwenzhang hypomethylationofcntfraisassociatedwithproliferationandpoorprognosisinlowergradegliomas AT romelaireneramos hypomethylationofcntfraisassociatedwithproliferationandpoorprognosisinlowergradegliomas AT haibozhang hypomethylationofcntfraisassociatedwithproliferationandpoorprognosisinlowergradegliomas AT chunjieli hypomethylationofcntfraisassociatedwithproliferationandpoorprognosisinlowergradegliomas AT danye hypomethylationofcntfraisassociatedwithproliferationandpoorprognosisinlowergradegliomas AT jianshengkang hypomethylationofcntfraisassociatedwithproliferationandpoorprognosisinlowergradegliomas AT diegommarzese hypomethylationofcntfraisassociatedwithproliferationandpoorprognosisinlowergradegliomas AT davesbhoon hypomethylationofcntfraisassociatedwithproliferationandpoorprognosisinlowergradegliomas AT weihua hypomethylationofcntfraisassociatedwithproliferationandpoorprognosisinlowergradegliomas
_version_	1718393915976974336

Hypomethylation of CNTFRα is associated with proliferation and poor prognosis in lower grade gliomas

Ejemplares similares