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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| Item Type: | Tesi di dottorato |
|---|---|
| Resource language: | 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 |
| 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 |
| 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 |
Collection description
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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