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TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival
BACKGROUND: Human gliomas are a heterogeneous group of primary malignant brain tumors whose molecular pathogenesis is not yet solved. In this regard, a major research effort has been directed at identifying novel specific glioma-associated genes. Here, we investigated the effect of TRIM8 gene in gli...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468980/ https://www.ncbi.nlm.nih.gov/pubmed/26077989 http://dx.doi.org/10.1186/s12885-015-1449-9 |
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author | Micale, Lucia Fusco, Carmela Fontana, Andrea Barbano, Raffaela Augello, Bartolomeo De Nittis, Pasquelena Copetti, Massimiliano Pellico, Maria Teresa Mandriani, Barbara Cocciadiferro, Dario Parrella, Paola Fazio, Vito Michele Dimitri, Lucia Maria Cecilia D’Angelo, Vincenzo Novielli, Chiara Larizza, Lidia Daga, Antonio Merla, Giuseppe |
author_facet | Micale, Lucia Fusco, Carmela Fontana, Andrea Barbano, Raffaela Augello, Bartolomeo De Nittis, Pasquelena Copetti, Massimiliano Pellico, Maria Teresa Mandriani, Barbara Cocciadiferro, Dario Parrella, Paola Fazio, Vito Michele Dimitri, Lucia Maria Cecilia D’Angelo, Vincenzo Novielli, Chiara Larizza, Lidia Daga, Antonio Merla, Giuseppe |
author_sort | Micale, Lucia |
collection | PubMed |
description | BACKGROUND: Human gliomas are a heterogeneous group of primary malignant brain tumors whose molecular pathogenesis is not yet solved. In this regard, a major research effort has been directed at identifying novel specific glioma-associated genes. Here, we investigated the effect of TRIM8 gene in glioma. METHODS: TRIM8 transcriptional level was profiled in our own glioma cases collection by qPCR and confirmed in the independent TCGA glioma cohort. The association between TRIM8 expression and Overall Survival and Progression-free Survival in TCGA cohort was determined by using uni-multivariable Cox regression analysis. The effect of TRIM8 on patient glioma cell proliferation was evaluated by performing MTT and clonogenic assays. The mechanisms causing the reduction of TRIM8 expression were explored by using qPCR and in vitro assays. RESULTS: We showed that TRIM8 expression correlates with unfavorable clinical outcome in glioma patients. We found that a restored TRIM8 expression induced a significant reduction of clonogenic potential in U87MG and patient’s glioblastoma cells. Finally we provide experimental evidences showing that miR-17 directly targets the 3′ UTR of TRIM8 and post-transcriptionally represses the expression of TRIM8. CONCLUSIONS: Our study provides evidences that TRIM8 may participate in the carcinogenesis and progression of glioma and that the transcriptional repression of TRIM8 might have potential value for predicting poor prognosis in glioma patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1449-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4468980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44689802015-06-17 TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival Micale, Lucia Fusco, Carmela Fontana, Andrea Barbano, Raffaela Augello, Bartolomeo De Nittis, Pasquelena Copetti, Massimiliano Pellico, Maria Teresa Mandriani, Barbara Cocciadiferro, Dario Parrella, Paola Fazio, Vito Michele Dimitri, Lucia Maria Cecilia D’Angelo, Vincenzo Novielli, Chiara Larizza, Lidia Daga, Antonio Merla, Giuseppe BMC Cancer Research Article BACKGROUND: Human gliomas are a heterogeneous group of primary malignant brain tumors whose molecular pathogenesis is not yet solved. In this regard, a major research effort has been directed at identifying novel specific glioma-associated genes. Here, we investigated the effect of TRIM8 gene in glioma. METHODS: TRIM8 transcriptional level was profiled in our own glioma cases collection by qPCR and confirmed in the independent TCGA glioma cohort. The association between TRIM8 expression and Overall Survival and Progression-free Survival in TCGA cohort was determined by using uni-multivariable Cox regression analysis. The effect of TRIM8 on patient glioma cell proliferation was evaluated by performing MTT and clonogenic assays. The mechanisms causing the reduction of TRIM8 expression were explored by using qPCR and in vitro assays. RESULTS: We showed that TRIM8 expression correlates with unfavorable clinical outcome in glioma patients. We found that a restored TRIM8 expression induced a significant reduction of clonogenic potential in U87MG and patient’s glioblastoma cells. Finally we provide experimental evidences showing that miR-17 directly targets the 3′ UTR of TRIM8 and post-transcriptionally represses the expression of TRIM8. CONCLUSIONS: Our study provides evidences that TRIM8 may participate in the carcinogenesis and progression of glioma and that the transcriptional repression of TRIM8 might have potential value for predicting poor prognosis in glioma patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1449-9) contains supplementary material, which is available to authorized users. BioMed Central 2015-06-16 /pmc/articles/PMC4468980/ /pubmed/26077989 http://dx.doi.org/10.1186/s12885-015-1449-9 Text en © Micale et al. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Micale, Lucia Fusco, Carmela Fontana, Andrea Barbano, Raffaela Augello, Bartolomeo De Nittis, Pasquelena Copetti, Massimiliano Pellico, Maria Teresa Mandriani, Barbara Cocciadiferro, Dario Parrella, Paola Fazio, Vito Michele Dimitri, Lucia Maria Cecilia D’Angelo, Vincenzo Novielli, Chiara Larizza, Lidia Daga, Antonio Merla, Giuseppe TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival |
title | TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival |
title_full | TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival |
title_fullStr | TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival |
title_full_unstemmed | TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival |
title_short | TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival |
title_sort | trim8 downregulation in glioma affects cell proliferation and it is associated with patients survival |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468980/ https://www.ncbi.nlm.nih.gov/pubmed/26077989 http://dx.doi.org/10.1186/s12885-015-1449-9 |
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