MicroRNAs Expression Profile in MN1-Altered Astroblastoma

Background/Objectives: Astroblastoma is a rare glial neoplasm more frequent in young female patients, with unclear clinical behaviors and outcomes. The diagnostic molecular alteration is a rearrangement of the Meningioma 1 (<i>MN1</i>) gene. MicroRNAs (miRNAs) are important gene expressi...

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Main Authors: Francesca Gianno, Evelina Miele, Claudia Sabato, Elisabetta Ferretti, Simone Minasi, Francesca Romana Buttarelli, Debora Salerno, Natalia Pediconi, Giuseppe Rubens Pascucci, Francesca Guerrieri, Andrea Ciolfi, Simone Pizzi, Maura Massimino, Veronica Biassoni, Elisabetta Schiavello, Marco Gessi, Sofia Asioli, Angela Mastronuzzi, Antonio d’Amati, Giuseppina Catanzaro, Elisabetta Viscardi, David Capper, Felice Giangaspero, Manila Antonelli
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/1/112
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author Francesca Gianno
Evelina Miele
Claudia Sabato
Elisabetta Ferretti
Simone Minasi
Francesca Romana Buttarelli
Debora Salerno
Natalia Pediconi
Giuseppe Rubens Pascucci
Francesca Guerrieri
Andrea Ciolfi
Simone Pizzi
Maura Massimino
Veronica Biassoni
Elisabetta Schiavello
Marco Gessi
Sofia Asioli
Angela Mastronuzzi
Antonio d’Amati
Giuseppina Catanzaro
Elisabetta Viscardi
David Capper
Felice Giangaspero
Manila Antonelli
author_facet Francesca Gianno
Evelina Miele
Claudia Sabato
Elisabetta Ferretti
Simone Minasi
Francesca Romana Buttarelli
Debora Salerno
Natalia Pediconi
Giuseppe Rubens Pascucci
Francesca Guerrieri
Andrea Ciolfi
Simone Pizzi
Maura Massimino
Veronica Biassoni
Elisabetta Schiavello
Marco Gessi
Sofia Asioli
Angela Mastronuzzi
Antonio d’Amati
Giuseppina Catanzaro
Elisabetta Viscardi
David Capper
Felice Giangaspero
Manila Antonelli
author_sort Francesca Gianno
collection DOAJ
description Background/Objectives: Astroblastoma is a rare glial neoplasm more frequent in young female patients, with unclear clinical behaviors and outcomes. The diagnostic molecular alteration is a rearrangement of the Meningioma 1 (<i>MN1</i>) gene. MicroRNAs (miRNAs) are important gene expression regulators with strong implications in biological processes. Here, we investigated microRNA expression, regulation, and biological processes correlated to target genes of deregulated miRNAs in MN1-altered astroblastoma. Methods: A cohort of 14 tumor samples, histologically classified as astroblastoma, was retrospectively collected and analyzed through their DNA methylation profiles. MiRNA expression profiles were then detected on <i>MN1</i>-altered astroblastomas (<i>n</i> = 8) and normal brain controls (<i>n</i> = 2) by Nanostring technology and validated by RT-qPCR; then, the expression of deregulated miRNAs was correlated with clinical-pathological characteristics. Subsequently, the methylation status of promoters of deregulated miRNAs was investigated through a methylation profiling microarray. Finally, bioinformatics analysis was conducted to explore the biological processes (BPs) and target genes of differentially expressed miRNAs. Results: Eight <i>MN</i>-altered astroblastoma were identified. Thirty-nine miRNAs were deregulated in tumor samples compared to normal brain tissue. Downregulated microRNAs exhibited an association with an increased risk of recurrence. The promoter methylation status was investigated in 32/39 miRNAs: 14/32 were epigenetically deregulated. None of them were genetically regulated. Conclusions: <i>MN1</i>-altered astroblastomas have an miRNA expression signature that identifies specific BPs and pathways. Our findings suggested that the involved pathways could be associated with clinical and pathological characteristics of MN1-altered astroblastomas. Also, the biology of this rare tumor could have potential implications on prognostic markers and therapy.
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spelling doaj-art-5e29d8d91bc44b5cacf94a77dbc509d62025-01-24T13:24:03ZengMDPI AGBiomedicines2227-90592025-01-0113111210.3390/biomedicines13010112MicroRNAs Expression Profile in MN1-Altered AstroblastomaFrancesca Gianno0Evelina Miele1Claudia Sabato2Elisabetta Ferretti3Simone Minasi4Francesca Romana Buttarelli5Debora Salerno6Natalia Pediconi7Giuseppe Rubens Pascucci8Francesca Guerrieri9Andrea Ciolfi10Simone Pizzi11Maura Massimino12Veronica Biassoni13Elisabetta Schiavello14Marco Gessi15Sofia Asioli16Angela Mastronuzzi17Antonio d’Amati18Giuseppina Catanzaro19Elisabetta Viscardi20David Capper21Felice Giangaspero22Manila Antonelli23Department of Radiological, Oncological and Anatomo-Pathological Sciences, University Sapienza of Rome, 00161 Rome, ItalyHematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Radiological, Oncological and Anatomo-Pathological Sciences, University Sapienza of Rome, 00161 Rome, ItalyDepartment of Radiological, Oncological and Anatomo-Pathological Sciences, University Sapienza of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, 00161 Rome, ItalyCenter for Life Nano- & Neuro-Science, Fondazione Istituto Italiano di Tecnologia (IIT), 16161 Rome, ItalyResearch Unit of Clinical Immunology and Vaccinology, Academic Department of Pediatrics, Bambino Gesù Children’s Hospital, 00165 Rome, ItalyUMR INSERM U1052/CNRS 5286, Cancer Research Center of Lyon, 69008 Lyon, FranceMolecular Genetics and Functional Genomics, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyInstitute of Biosciences and Bioresources, National Research Council, 06128 Perugia, ItalyPediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milano, ItalyPediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milano, ItalyPediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milano, ItalyDepartment of Woman and Child Health Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, ItalyIRCCS Istituto di Scienze Neurologiche di Bologna, 40139 Bologna, ItalyHematology/Oncology, Cell Therapy, Gene Therapies and Hemopoietic Transplant, 586724 Bambino Gesù Children’s Hospital, 00165 Rome, ItalyDepartment of Basic Medical Sciences, Neuroscience, and Sensory Organs, University of Bari School of Medicine, 70121 Bari, ItalyDepartment of Life Science, Health, and Health Professions, Link Campus University, 00165 Rome, ItalyPediatric Oncology Unit, Padova University, 35122 Padova, ItalyCharité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt, 10117 Berlin, GermanyDepartment of Radiological, Oncological and Anatomo-Pathological Sciences, University Sapienza of Rome, 00161 Rome, ItalyDepartment of Radiological, Oncological and Anatomo-Pathological Sciences, University Sapienza of Rome, 00161 Rome, ItalyBackground/Objectives: Astroblastoma is a rare glial neoplasm more frequent in young female patients, with unclear clinical behaviors and outcomes. The diagnostic molecular alteration is a rearrangement of the Meningioma 1 (<i>MN1</i>) gene. MicroRNAs (miRNAs) are important gene expression regulators with strong implications in biological processes. Here, we investigated microRNA expression, regulation, and biological processes correlated to target genes of deregulated miRNAs in MN1-altered astroblastoma. Methods: A cohort of 14 tumor samples, histologically classified as astroblastoma, was retrospectively collected and analyzed through their DNA methylation profiles. MiRNA expression profiles were then detected on <i>MN1</i>-altered astroblastomas (<i>n</i> = 8) and normal brain controls (<i>n</i> = 2) by Nanostring technology and validated by RT-qPCR; then, the expression of deregulated miRNAs was correlated with clinical-pathological characteristics. Subsequently, the methylation status of promoters of deregulated miRNAs was investigated through a methylation profiling microarray. Finally, bioinformatics analysis was conducted to explore the biological processes (BPs) and target genes of differentially expressed miRNAs. Results: Eight <i>MN</i>-altered astroblastoma were identified. Thirty-nine miRNAs were deregulated in tumor samples compared to normal brain tissue. Downregulated microRNAs exhibited an association with an increased risk of recurrence. The promoter methylation status was investigated in 32/39 miRNAs: 14/32 were epigenetically deregulated. None of them were genetically regulated. Conclusions: <i>MN1</i>-altered astroblastomas have an miRNA expression signature that identifies specific BPs and pathways. Our findings suggested that the involved pathways could be associated with clinical and pathological characteristics of MN1-altered astroblastomas. Also, the biology of this rare tumor could have potential implications on prognostic markers and therapy.https://www.mdpi.com/2227-9059/13/1/112astroblastomamicroRNAmiRNA expressionbiological processesepigeneticmethylation
spellingShingle Francesca Gianno
Evelina Miele
Claudia Sabato
Elisabetta Ferretti
Simone Minasi
Francesca Romana Buttarelli
Debora Salerno
Natalia Pediconi
Giuseppe Rubens Pascucci
Francesca Guerrieri
Andrea Ciolfi
Simone Pizzi
Maura Massimino
Veronica Biassoni
Elisabetta Schiavello
Marco Gessi
Sofia Asioli
Angela Mastronuzzi
Antonio d’Amati
Giuseppina Catanzaro
Elisabetta Viscardi
David Capper
Felice Giangaspero
Manila Antonelli
MicroRNAs Expression Profile in MN1-Altered Astroblastoma
Biomedicines
astroblastoma
microRNA
miRNA expression
biological processes
epigenetic
methylation
title MicroRNAs Expression Profile in MN1-Altered Astroblastoma
title_full MicroRNAs Expression Profile in MN1-Altered Astroblastoma
title_fullStr MicroRNAs Expression Profile in MN1-Altered Astroblastoma
title_full_unstemmed MicroRNAs Expression Profile in MN1-Altered Astroblastoma
title_short MicroRNAs Expression Profile in MN1-Altered Astroblastoma
title_sort micrornas expression profile in mn1 altered astroblastoma
topic astroblastoma
microRNA
miRNA expression
biological processes
epigenetic
methylation
url https://www.mdpi.com/2227-9059/13/1/112
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