The miRNA Content of Exosomes Released from the Glioma Microenvironment Can Affect Malignant Progression

Low-grade gliomas (LGG) are infiltrative primary brain tumors that in 70% of the cases undergo anaplastic transformation, deeply affecting prognosis. However, the timing of progression is heterogeneous. Recently, the tumor microenvironment (TME) has gained much attention either as prognostic factor...

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Main Authors: Federica Caponnetto, Emiliano Dalla, Damiano Mangoni, Silvano Piazza, Slobodanka Radovic, Tamara Ius, Miran Skrap, Carla Di Loreto, Antonio Paolo Beltrami, Ivana Manini, Daniela Cesselli
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/8/12/564
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author Federica Caponnetto
Emiliano Dalla
Damiano Mangoni
Silvano Piazza
Slobodanka Radovic
Tamara Ius
Miran Skrap
Carla Di Loreto
Antonio Paolo Beltrami
Ivana Manini
Daniela Cesselli
author_facet Federica Caponnetto
Emiliano Dalla
Damiano Mangoni
Silvano Piazza
Slobodanka Radovic
Tamara Ius
Miran Skrap
Carla Di Loreto
Antonio Paolo Beltrami
Ivana Manini
Daniela Cesselli
author_sort Federica Caponnetto
collection DOAJ
description Low-grade gliomas (LGG) are infiltrative primary brain tumors that in 70% of the cases undergo anaplastic transformation, deeply affecting prognosis. However, the timing of progression is heterogeneous. Recently, the tumor microenvironment (TME) has gained much attention either as prognostic factor or therapeutic target. Through the release of extracellular vesicles, the TME contributes to tumor progression by transferring bioactive molecules such as microRNA. The aim of the study was to take advantage of glioma-associated stem cells (GASC), an in vitro model of the glioma microenvironment endowed with a prognostic significance, and their released exosomes, to investigate the possible role of exosome miRNAs in favoring the anaplastic transformation of LGG. Therefore, by deep sequencing, we analyzed and compared the miRNA profile of GASC and exosomes obtained from LGG patients characterized by different prognosis. Results showed that exosomes presented a different signature, when compared to their cellular counterpart and that, although sharing several miRNAs, exosomes of patients with a bad prognosis, selectively expressed some miRNAs possibly responsible for the more aggressive phenotype. These findings get insights into the value of TME and exosomes as potential biomarkers for precision medicine approaches aimed at improving LGG prognostic stratification and therapeutic strategies.
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spelling doaj.art-45b67cb983e24d7bbb9de4eaf44c48872023-11-20T23:18:05ZengMDPI AGBiomedicines2227-90592020-12-0181256410.3390/biomedicines8120564The miRNA Content of Exosomes Released from the Glioma Microenvironment Can Affect Malignant ProgressionFederica Caponnetto0Emiliano Dalla1Damiano Mangoni2Silvano Piazza3Slobodanka Radovic4Tamara Ius5Miran Skrap6Carla Di Loreto7Antonio Paolo Beltrami8Ivana Manini9Daniela Cesselli10Department of Medicine, University of Udine, 33100 Udine, ItalyDepartment of Medicine, University of Udine, 33100 Udine, ItalyCentral RNA Laboratory, Istituto Italiano di Tecnologia (IIT), 16163 Genova, ItalyInternational Center for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, ItalyIGA Technology Services, S.R.L., 33100 Udine, ItalyNeurosurgery Unit, Department of Neurosciences, University Hospital of Udine, 33100 Udine, ItalyNeurosurgery Unit, Department of Neurosciences, University Hospital of Udine, 33100 Udine, ItalyDepartment of Medicine, University of Udine, 33100 Udine, ItalyDepartment of Medicine, University of Udine, 33100 Udine, ItalyInstitute of Pathology, University Hospital of Udine, 33100 Udine, ItalyDepartment of Medicine, University of Udine, 33100 Udine, ItalyLow-grade gliomas (LGG) are infiltrative primary brain tumors that in 70% of the cases undergo anaplastic transformation, deeply affecting prognosis. However, the timing of progression is heterogeneous. Recently, the tumor microenvironment (TME) has gained much attention either as prognostic factor or therapeutic target. Through the release of extracellular vesicles, the TME contributes to tumor progression by transferring bioactive molecules such as microRNA. The aim of the study was to take advantage of glioma-associated stem cells (GASC), an in vitro model of the glioma microenvironment endowed with a prognostic significance, and their released exosomes, to investigate the possible role of exosome miRNAs in favoring the anaplastic transformation of LGG. Therefore, by deep sequencing, we analyzed and compared the miRNA profile of GASC and exosomes obtained from LGG patients characterized by different prognosis. Results showed that exosomes presented a different signature, when compared to their cellular counterpart and that, although sharing several miRNAs, exosomes of patients with a bad prognosis, selectively expressed some miRNAs possibly responsible for the more aggressive phenotype. These findings get insights into the value of TME and exosomes as potential biomarkers for precision medicine approaches aimed at improving LGG prognostic stratification and therapeutic strategies.https://www.mdpi.com/2227-9059/8/12/564exosomestumor microenvironmentmicroRNAlow-grade gliomasstratification criteria
spellingShingle Federica Caponnetto
Emiliano Dalla
Damiano Mangoni
Silvano Piazza
Slobodanka Radovic
Tamara Ius
Miran Skrap
Carla Di Loreto
Antonio Paolo Beltrami
Ivana Manini
Daniela Cesselli
The miRNA Content of Exosomes Released from the Glioma Microenvironment Can Affect Malignant Progression
Biomedicines
exosomes
tumor microenvironment
microRNA
low-grade gliomas
stratification criteria
title The miRNA Content of Exosomes Released from the Glioma Microenvironment Can Affect Malignant Progression
title_full The miRNA Content of Exosomes Released from the Glioma Microenvironment Can Affect Malignant Progression
title_fullStr The miRNA Content of Exosomes Released from the Glioma Microenvironment Can Affect Malignant Progression
title_full_unstemmed The miRNA Content of Exosomes Released from the Glioma Microenvironment Can Affect Malignant Progression
title_short The miRNA Content of Exosomes Released from the Glioma Microenvironment Can Affect Malignant Progression
title_sort mirna content of exosomes released from the glioma microenvironment can affect malignant progression
topic exosomes
tumor microenvironment
microRNA
low-grade gliomas
stratification criteria
url https://www.mdpi.com/2227-9059/8/12/564
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