Fiore, Danilo
(2015)
Survival in glioblastoma patients is predicted by miR-340, that regulates key cancer hallmarks by inhibiting NRAS.
[Tesi di dottorato]
Item Type: |
Tesi di dottorato
|
Lingua: |
English |
Title: |
Survival in glioblastoma patients is predicted by miR-340, that regulates key cancer hallmarks by inhibiting NRAS |
Creators: |
Creators | Email |
---|
Fiore, Danilo | danilo.fiore@unina.it |
|
Date: |
31 March 2015 |
Number of Pages: |
102 |
Institution: |
Università degli Studi di Napoli Federico II |
Department: |
Medicina Molecolare e Biotecnologie Mediche |
Scuola di dottorato: |
Medicina molecolare |
Dottorato: |
Patologia e fisiopatologia molecolare |
Ciclo di dottorato: |
27 |
Coordinatore del Corso di dottorato: |
nome | email |
---|
Avvedimento, Vittorio Enrico | vittorioenrico.avvedimento@unina.it |
|
Tutor: |
nome | email |
---|
Condorelli, Gerolama | UNSPECIFIED |
|
Date: |
31 March 2015 |
Number of Pages: |
102 |
Uncontrolled Keywords: |
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 |
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Date Deposited: |
10 Apr 2015 11:01 |
Last Modified: |
07 May 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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