Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment

Ectopic epigenetic mechanisms play important roles in facilitating tumorigenesis. Here, we first demonstrated that ANKDD1A is a functional tumor suppressor gene, especially in the hypoxia microenvironment. ANKDD1A directly interacts with FIH1 and inhibits the transcriptional activity of HIF1α by upr...

Descripción completa

Detalles Bibliográficos
Autores principales: Feng, Jianbo, Zhang, Yan, She, Xiaoling, Sun, Yingnan, Fan, Li, Ren, Xing, Fu, Haijuan, Liu, Changhong, Li, Peiyao, Zhao, Chunhua, Liu, Qiang, Liu, Qing, Li, Guiyuan, Wu, Minghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318269/
https://www.ncbi.nlm.nih.gov/pubmed/30082910
http://dx.doi.org/10.1038/s41388-018-0423-9
_version_ 1783384843022761984
author Feng, Jianbo
Zhang, Yan
She, Xiaoling
Sun, Yingnan
Fan, Li
Ren, Xing
Fu, Haijuan
Liu, Changhong
Li, Peiyao
Zhao, Chunhua
Liu, Qiang
Liu, Qing
Li, Guiyuan
Wu, Minghua
author_facet Feng, Jianbo
Zhang, Yan
She, Xiaoling
Sun, Yingnan
Fan, Li
Ren, Xing
Fu, Haijuan
Liu, Changhong
Li, Peiyao
Zhao, Chunhua
Liu, Qiang
Liu, Qing
Li, Guiyuan
Wu, Minghua
author_sort Feng, Jianbo
collection PubMed
description Ectopic epigenetic mechanisms play important roles in facilitating tumorigenesis. Here, we first demonstrated that ANKDD1A is a functional tumor suppressor gene, especially in the hypoxia microenvironment. ANKDD1A directly interacts with FIH1 and inhibits the transcriptional activity of HIF1α by upregulating FIH1. In addition, ANKDD1A decreases the half-life of HIF1α by upregulating FIH1, decreases glucose uptake and lactate production, inhibits glioblastoma multiforme (GBM) autophagy, and induces apoptosis in GBM cells under hypoxia. Moreover, ANKDD1A is highly frequently methylated in GBM. The tumor-specific methylation of ANKDD1A indicates that it could be used as a potential epigenetic biomarker as well as a possible therapeutic target.
format Online
Article
Text
id pubmed-6318269
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-63182692019-01-07 Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment Feng, Jianbo Zhang, Yan She, Xiaoling Sun, Yingnan Fan, Li Ren, Xing Fu, Haijuan Liu, Changhong Li, Peiyao Zhao, Chunhua Liu, Qiang Liu, Qing Li, Guiyuan Wu, Minghua Oncogene Article Ectopic epigenetic mechanisms play important roles in facilitating tumorigenesis. Here, we first demonstrated that ANKDD1A is a functional tumor suppressor gene, especially in the hypoxia microenvironment. ANKDD1A directly interacts with FIH1 and inhibits the transcriptional activity of HIF1α by upregulating FIH1. In addition, ANKDD1A decreases the half-life of HIF1α by upregulating FIH1, decreases glucose uptake and lactate production, inhibits glioblastoma multiforme (GBM) autophagy, and induces apoptosis in GBM cells under hypoxia. Moreover, ANKDD1A is highly frequently methylated in GBM. The tumor-specific methylation of ANKDD1A indicates that it could be used as a potential epigenetic biomarker as well as a possible therapeutic target. Nature Publishing Group UK 2018-08-06 2019 /pmc/articles/PMC6318269/ /pubmed/30082910 http://dx.doi.org/10.1038/s41388-018-0423-9 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Feng, Jianbo
Zhang, Yan
She, Xiaoling
Sun, Yingnan
Fan, Li
Ren, Xing
Fu, Haijuan
Liu, Changhong
Li, Peiyao
Zhao, Chunhua
Liu, Qiang
Liu, Qing
Li, Guiyuan
Wu, Minghua
Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment
title Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment
title_full Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment
title_fullStr Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment
title_full_unstemmed Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment
title_short Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment
title_sort hypermethylated gene ankdd1a is a candidate tumor suppressor that interacts with fih1 and decreases hif1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318269/
https://www.ncbi.nlm.nih.gov/pubmed/30082910
http://dx.doi.org/10.1038/s41388-018-0423-9
work_keys_str_mv AT fengjianbo hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment
AT zhangyan hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment
AT shexiaoling hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment
AT sunyingnan hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment
AT fanli hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment
AT renxing hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment
AT fuhaijuan hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment
AT liuchanghong hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment
AT lipeiyao hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment
AT zhaochunhua hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment
AT liuqiang hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment
AT liuqing hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment
AT liguiyuan hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment
AT wuminghua hypermethylatedgeneankdd1aisacandidatetumorsuppressorthatinteractswithfih1anddecreaseshif1astabilitytoinhibitcellautophagyintheglioblastomamultiformehypoxiamicroenvironment

Ejemplares similares