Cargando…
Analysis of the inhibitors of apoptosis identifies BIRC3 as a facilitator of malignant progression in glioma
Gliomas, the most common primary brain tumor in humans, include a spectrum of disease. High-grade gliomas (HGG), such as glioblastoma, may arise from low-grade gliomas (LGG) that have a more indolent course. The process of malignant transformation (MT) of LGG to HGG is poorly understood but likely i...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355046/ https://www.ncbi.nlm.nih.gov/pubmed/27074575 http://dx.doi.org/10.18632/oncotarget.8657 |
_version_ | 1782515449835028480 |
---|---|
author | Gressot, Loyola V. Doucette, Tiffany Yang, Yuhui Fuller, Gregory N. Manyam, Ganiraju Rao, Arvind Latha, Khatri Rao, Ganesh |
author_facet | Gressot, Loyola V. Doucette, Tiffany Yang, Yuhui Fuller, Gregory N. Manyam, Ganiraju Rao, Arvind Latha, Khatri Rao, Ganesh |
author_sort | Gressot, Loyola V. |
collection | PubMed |
description | Gliomas, the most common primary brain tumor in humans, include a spectrum of disease. High-grade gliomas (HGG), such as glioblastoma, may arise from low-grade gliomas (LGG) that have a more indolent course. The process of malignant transformation (MT) of LGG to HGG is poorly understood but likely involves the activation of signaling programs that suppress apoptosis. We previously showed that Survivin (BIRC5) plays a role in malignant progression of glioma. Here, we investigated the role of the remaining members of the Inhibitors of Apoptosis (IAP) family on promoting MT in glioma. Utilizing expression data from the cancer genome atlas (TCGA), we identified BIRC3 as a key facilitator of MT from LGG to HGG. TCGA HGGs with high expression of BIRC 3 demonstrated a survival disadvantage and expression levels of BIRC3 were also significantly higher in TCGA HGG compared to TCGA LGG cases. We validated our findings from TCGA by using matched human specimens to show that BIRC expression is increased in HGG compared to their precursor LGG lesions. Using a unique murine model of glioma, we show that overexpression of BIRC3 promotes higher grade glioma and significantly reduces tumor-free survival in mice. |
format | Online Article Text |
id | pubmed-5355046 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53550462017-04-15 Analysis of the inhibitors of apoptosis identifies BIRC3 as a facilitator of malignant progression in glioma Gressot, Loyola V. Doucette, Tiffany Yang, Yuhui Fuller, Gregory N. Manyam, Ganiraju Rao, Arvind Latha, Khatri Rao, Ganesh Oncotarget Research Paper Gliomas, the most common primary brain tumor in humans, include a spectrum of disease. High-grade gliomas (HGG), such as glioblastoma, may arise from low-grade gliomas (LGG) that have a more indolent course. The process of malignant transformation (MT) of LGG to HGG is poorly understood but likely involves the activation of signaling programs that suppress apoptosis. We previously showed that Survivin (BIRC5) plays a role in malignant progression of glioma. Here, we investigated the role of the remaining members of the Inhibitors of Apoptosis (IAP) family on promoting MT in glioma. Utilizing expression data from the cancer genome atlas (TCGA), we identified BIRC3 as a key facilitator of MT from LGG to HGG. TCGA HGGs with high expression of BIRC 3 demonstrated a survival disadvantage and expression levels of BIRC3 were also significantly higher in TCGA HGG compared to TCGA LGG cases. We validated our findings from TCGA by using matched human specimens to show that BIRC expression is increased in HGG compared to their precursor LGG lesions. Using a unique murine model of glioma, we show that overexpression of BIRC3 promotes higher grade glioma and significantly reduces tumor-free survival in mice. Impact Journals LLC 2016-04-08 /pmc/articles/PMC5355046/ /pubmed/27074575 http://dx.doi.org/10.18632/oncotarget.8657 Text en Copyright: © 2017 Gressot et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Gressot, Loyola V. Doucette, Tiffany Yang, Yuhui Fuller, Gregory N. Manyam, Ganiraju Rao, Arvind Latha, Khatri Rao, Ganesh Analysis of the inhibitors of apoptosis identifies BIRC3 as a facilitator of malignant progression in glioma |
title | Analysis of the inhibitors of apoptosis identifies BIRC3 as a facilitator of malignant progression in glioma |
title_full | Analysis of the inhibitors of apoptosis identifies BIRC3 as a facilitator of malignant progression in glioma |
title_fullStr | Analysis of the inhibitors of apoptosis identifies BIRC3 as a facilitator of malignant progression in glioma |
title_full_unstemmed | Analysis of the inhibitors of apoptosis identifies BIRC3 as a facilitator of malignant progression in glioma |
title_short | Analysis of the inhibitors of apoptosis identifies BIRC3 as a facilitator of malignant progression in glioma |
title_sort | analysis of the inhibitors of apoptosis identifies birc3 as a facilitator of malignant progression in glioma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355046/ https://www.ncbi.nlm.nih.gov/pubmed/27074575 http://dx.doi.org/10.18632/oncotarget.8657 |
work_keys_str_mv | AT gressotloyolav analysisoftheinhibitorsofapoptosisidentifiesbirc3asafacilitatorofmalignantprogressioninglioma AT doucettetiffany analysisoftheinhibitorsofapoptosisidentifiesbirc3asafacilitatorofmalignantprogressioninglioma AT yangyuhui analysisoftheinhibitorsofapoptosisidentifiesbirc3asafacilitatorofmalignantprogressioninglioma AT fullergregoryn analysisoftheinhibitorsofapoptosisidentifiesbirc3asafacilitatorofmalignantprogressioninglioma AT manyamganiraju analysisoftheinhibitorsofapoptosisidentifiesbirc3asafacilitatorofmalignantprogressioninglioma AT raoarvind analysisoftheinhibitorsofapoptosisidentifiesbirc3asafacilitatorofmalignantprogressioninglioma AT lathakhatri analysisoftheinhibitorsofapoptosisidentifiesbirc3asafacilitatorofmalignantprogressioninglioma AT raoganesh analysisoftheinhibitorsofapoptosisidentifiesbirc3asafacilitatorofmalignantprogressioninglioma |