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miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS

Glioblastoma is the most common primary brain tumor in adults; with a survival rate of 12 months from diagnosis. However, a small subgroup of patients, termed long-term survivors (LTS), has a survival rate longer then 12–14 months. There is thus increasing interest in the identification of molecular...

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Autores principales: Fiore, Danilo, Donnarumma, Elvira, Roscigno, Giuseppina, Iaboni, Margherita, Russo, Valentina, Affinito, Alessandra, Adamo, Assunta, De Martino, Fabio, Quintavalle, Cristina, Romano, Giulia, Greco, Adelaide, Soini, Ylermi, Brunetti, Arturo, Croce, Carlo M., Condorelli, Gerolama
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991399/
https://www.ncbi.nlm.nih.gov/pubmed/26799668
http://dx.doi.org/10.18632/oncotarget.6968
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author Fiore, Danilo
Donnarumma, Elvira
Roscigno, Giuseppina
Iaboni, Margherita
Russo, Valentina
Affinito, Alessandra
Adamo, Assunta
De Martino, Fabio
Quintavalle, Cristina
Romano, Giulia
Greco, Adelaide
Soini, Ylermi
Brunetti, Arturo
Croce, Carlo M.
Condorelli, Gerolama
author_facet Fiore, Danilo
Donnarumma, Elvira
Roscigno, Giuseppina
Iaboni, Margherita
Russo, Valentina
Affinito, Alessandra
Adamo, Assunta
De Martino, Fabio
Quintavalle, Cristina
Romano, Giulia
Greco, Adelaide
Soini, Ylermi
Brunetti, Arturo
Croce, Carlo M.
Condorelli, Gerolama
author_sort Fiore, Danilo
collection PubMed
description Glioblastoma is the most common primary brain tumor in adults; with a survival rate of 12 months from diagnosis. However, a small subgroup of patients, termed long-term survivors (LTS), has a survival rate longer then 12–14 months. There is thus increasing interest in the identification of molecular signatures predicting glioblastoma prognosis and in how to improve the therapeutic approach. Here, we report miR-340 as prognostic tumor-suppressor microRNA for glioblastoma. We analyzed microRNA expression in > 500 glioblastoma patients and found that although miR-340 is strongly down-regulated in glioblastoma overall, it is up-regulated in LTS patients compared to short-term survivors (STS). Indeed, miR-340 expression predicted better prognosis in glioblastoma patients. Coherently, overexpression of miR-340 in glioblastoma cells was found to produce a tumor-suppressive activity. We identified NRAS mRNA as a critical, direct target of miR-340: in fact, miR-340 negatively influenced multiple aspects of glioblastoma tumorigenesis by down-regulating NRAS and downstream AKT and ERK pathways. Thus, we demonstrate that expression of miR-340 in glioblastoma is responsible for a strong tumor-suppressive effect in LTS patients by down-regulating NRAS. miR-340 may thus represent a novel marker for glioblastoma diagnosis and prognosis, and may be developed into a tool to improve treatment of glioblastoma.
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spelling pubmed-49913992016-09-01 miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS Fiore, Danilo Donnarumma, Elvira Roscigno, Giuseppina Iaboni, Margherita Russo, Valentina Affinito, Alessandra Adamo, Assunta De Martino, Fabio Quintavalle, Cristina Romano, Giulia Greco, Adelaide Soini, Ylermi Brunetti, Arturo Croce, Carlo M. Condorelli, Gerolama Oncotarget Research Paper Glioblastoma is the most common primary brain tumor in adults; with a survival rate of 12 months from diagnosis. However, a small subgroup of patients, termed long-term survivors (LTS), has a survival rate longer then 12–14 months. There is thus increasing interest in the identification of molecular signatures predicting glioblastoma prognosis and in how to improve the therapeutic approach. Here, we report miR-340 as prognostic tumor-suppressor microRNA for glioblastoma. We analyzed microRNA expression in > 500 glioblastoma patients and found that although miR-340 is strongly down-regulated in glioblastoma overall, it is up-regulated in LTS patients compared to short-term survivors (STS). Indeed, miR-340 expression predicted better prognosis in glioblastoma patients. Coherently, overexpression of miR-340 in glioblastoma cells was found to produce a tumor-suppressive activity. We identified NRAS mRNA as a critical, direct target of miR-340: in fact, miR-340 negatively influenced multiple aspects of glioblastoma tumorigenesis by down-regulating NRAS and downstream AKT and ERK pathways. Thus, we demonstrate that expression of miR-340 in glioblastoma is responsible for a strong tumor-suppressive effect in LTS patients by down-regulating NRAS. miR-340 may thus represent a novel marker for glioblastoma diagnosis and prognosis, and may be developed into a tool to improve treatment of glioblastoma. Impact Journals LLC 2016-01-21 /pmc/articles/PMC4991399/ /pubmed/26799668 http://dx.doi.org/10.18632/oncotarget.6968 Text en Copyright: © 2016 Fiore et al. http://creativecommons.org/licenses/by/2.5/ 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
Fiore, Danilo
Donnarumma, Elvira
Roscigno, Giuseppina
Iaboni, Margherita
Russo, Valentina
Affinito, Alessandra
Adamo, Assunta
De Martino, Fabio
Quintavalle, Cristina
Romano, Giulia
Greco, Adelaide
Soini, Ylermi
Brunetti, Arturo
Croce, Carlo M.
Condorelli, Gerolama
miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS
title miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS
title_full miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS
title_fullStr miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS
title_full_unstemmed miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS
title_short miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS
title_sort mir-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of nras
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991399/
https://www.ncbi.nlm.nih.gov/pubmed/26799668
http://dx.doi.org/10.18632/oncotarget.6968
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