Fiore, Danilo (2015) Survival in glioblastoma patients is predicted by miR-340, that regulates key cancer hallmarks by inhibiting NRAS. [Tesi di dottorato]

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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: Survival in glioblastoma patients is predicted by miR-340, that regulates key cancer hallmarks by inhibiting NRAS
Autori:
AutoreEmail
Fiore, Danilodanilo.fiore@unina.it
Data: 31 Marzo 2015
Numero di pagine: 102
Istituzione: Università degli Studi di Napoli Federico II
Dipartimento: Medicina Molecolare e Biotecnologie Mediche
Scuola di dottorato: Medicina molecolare
Dottorato: Patologia e fisiopatologia molecolare
Ciclo di dottorato: 27
Coordinatore del Corso di dottorato:
nomeemail
Avvedimento, Vittorio Enricovittorioenrico.avvedimento@unina.it
Tutor:
nomeemail
Condorelli, Gerolama[non definito]
Data: 31 Marzo 2015
Numero di pagine: 102
Parole chiave: Glioblastoma, microRNA, survival, NRAS
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/04 - Patologia generale
Aree tematiche (7° programma Quadro): SALUTE e TUTELA DEL CONSUMATORE > Biotecnologie, strumenti e tecnologie generiche per la salute umana
Depositato il: 10 Apr 2015 11:01
Ultima modifica: 07 Mag 2016 01:00
URI: http://www.fedoa.unina.it/id/eprint/10463
DOI: 10.6092/UNINA/FEDOA/10463

Abstract

Glioblastoma (GBM) is the most common primary brain tumor in adults, with a poor prognosis and a survival rate of only 12 months after diagnosis. Long-term survivors (LTS) are a small subgroup of glioblastoma patients characterized by a survival rate longer then 12-14 months. There is an increasing interest in the identification of molecular signatures to predict patient prognosis in GBM and delineate the best therapeutic approach. In this work, we reported miR-340 as a novel prognostic tumor-suppressor miRNA in glioblastoma. We analyzed miRNAs expression in two different cohorts of glioblastoma patients accounting for >500 patients, demonstrating that miR-340 is strongly down-regulated in glioblastoma, while is over-expressed in LTS patients compared to short term survivors (STS). Further, we demonstrated that miR-340 expression predicts a better prognosis of GBM patients. miR-340 overexpression in glioblastoma cells had a strong tumor-suppressive activity in vitro and in vivo in nude mice. Finally, we identified N-RAS as a direct critical target of miR-340, and demonstrated that, through N-RAS, miR-340 negatively influence multiple aspects of glioblastoma tumorigenesis, regulating AKT and ERKs pathways. Taken together, our data suggest that miR-340 is down-regulated in glioblastoma, where it exerts a strong tumor-suppressive effect by regulating N-RAS. Thus, miR-340 may represents a novel potential marker for the diagnosis, prognosis and treatment of GBM.

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