CINECA IRIS Institutional Research Information System
IRIS è il sistema di gestione integrata dei dati della ricerca (persone, progetti, pubblicazioni, attività) adottato dall'Università degli Studi di Torino.
AperTO è l'archivio istituzionale Open Access destinato a raccogliere, rendere visibile e conservare la produzione scientifica dell'Università degli Studi di Torino.
EnglishSystemic Anaplastic Large Cell Lymphoma represents a category of T-cell Non-Hodgkin Lymphoma further subdivided into two distinct entities (ALK+ and ALK-), based on the presence of ALK gene rearrangements. Among several pathways triggered by ALK signaling, constitutive activation of STAT3 is strictly required for ALK-mediated transformation and survival. Here we performed a genome-wide miRNA profiling and identified 48 miRNAs concordantly modulated by the inducible knock-down of ALK and STAT3. To evaluate the functional role of differentially expressed miRNAs, we forced their expression in ALK+ Anaplastic Large Cell Lymphoma cells, and monitored their influence after STAT3 depletion. We found that the expression of miR-17~92 cluster partially rescues STAT3 knock-down by sustaining proliferation and survival of ALK+ cells. Experiments in a xenograft mouse model indicated that forced expression of miR-17~92 interferes with STAT3 knock-down in vivo. High expression levels of miR-17~92 cluster resulted in down-regulation of BIM and TGFbetaRII proteins, suggesting that their targeting might mediate resistance to STAT3 knock-down in Anaplastic Large Cell Lymphoma cells. We speculate that miR-17~92 cluster is involved in the lymphomagenesis of STAT3+ ALCL, and that its inhibition might represent an alternative avenue to interfere with ALK signaling in Anaplastic Large Cell Lymphomas.
| Titolo: | STAT3-mediated activation of microRNA cluster 17~92 promotes proliferation and survival of ALK positive anaplastic large cell lymphoma. | |
| Autori Riconosciuti: | ||
| Autori: | Elisa Spaccarotella; Elisa Pellegrino; Manuela Ferracin; Cristina Ferreri; Giuditta Cuccuru; Cuiling Liu; Javeed Iqbal; Daniela Cantarella; Riccardo Taulli; Paolo Provero; Ferdinando Di Cunto; Enzo Medico; Massimo Negrini; Wing C. Chan; Giorgio Inghirami; Roberto Piva | |
| Data di pubblicazione: | 2014 | |
| Abstract: | Systemic Anaplastic Large Cell Lymphoma represents a category of T-cell Non-Hodgkin Lymphoma further subdivided into two distinct entities (ALK+ and ALK-), based on the presence of ALK gene rearrangements. Among several pathways triggered by ALK signaling, constitutive activation of STAT3 is strictly required for ALK-mediated transformation and survival. Here we performed a genome-wide miRNA profiling and identified 48 miRNAs concordantly modulated by the inducible knock-down of ALK and STAT3. To evaluate the functional role of differentially expressed miRNAs, we forced their expression in ALK+ Anaplastic Large Cell Lymphoma cells, and monitored their influence after STAT3 depletion. We found that the expression of miR-17~92 cluster partially rescues STAT3 knock-down by sustaining proliferation and survival of ALK+ cells. Experiments in a xenograft mouse model indicated that forced expression of miR-17~92 interferes with STAT3 knock-down in vivo. High expression levels of miR-17~92 cluster resulted in down-regulation of BIM and TGFbetaRII proteins, suggesting that their targeting might mediate resistance to STAT3 knock-down in Anaplastic Large Cell Lymphoma cells. We speculate that miR-17~92 cluster is involved in the lymphomagenesis of STAT3+ ALCL, and that its inhibition might represent an alternative avenue to interfere with ALK signaling in Anaplastic Large Cell Lymphomas. | |
| Volume: | 99 | |
| Fascicolo: | 1 | |
| Pagina iniziale: | 116 | |
| Pagina finale: | 124 | |
| Digital Object Identifier (DOI): | 10.3324/haematol.2013.088286 | |
| URL: | http://www.haematologica.org/content/99/1/116.long | |
| Parole Chiave: | PERIPHERAL T-CELL; SIGNALING PATHWAY; STAT3 ACTIVATION; DOWN-REGULATION; LUNG-CANCER; KINASE; EXPRESSION; TARGET; INHIBITOR; GENE | |
| Rivista: | HAEMATOLOGICA | |
| Appare nelle tipologie: | 03A-Articolo su Rivista |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| 2014-STAT3-mediated activation.pdf | PDF EDITORIALE | Open Access Visualizza/Apri |
Copyright © 2022