Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells (Articolo in rivista)

Type
Label
  • Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Alternative label
  • Ferretti E.; De Smaele E.; Miele E.; Laneve P.; Po A.; Pelloni M.; Paganelli A.; Di Marcotullio L.; Greco A.; Caffarelli E.; Screpanti I.; Bozzoni I.; Gulino A. (2008)
    Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells
    in EMBO journal (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Ferretti E.; De Smaele E.; Miele E.; Laneve P.; Po A.; Pelloni M.; Paganelli A.; Di Marcotullio L.; Greco A.; Caffarelli E.; Screpanti I.; Bozzoni I.; Gulino A. (literal)
Pagina inizio
  • 2616 (literal)
Pagina fine
  • 2627 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 27 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Ferretti E, Department of Experimental Medicine, Sapienza University, Roma De Smaele E, Department of Experimental Medicine, Sapienza University, Roma Miele E, Department of Experimental Medicine, Sapienza University, Roma Laneve P, Institute of Molecular Biology and Pathology, Consiglio Nazionale delle Ricerche, Sapienza University, Roma Po A, Department of Experimental Medicine, Sapienza University, Roma Pelloni M, Department of Experimental Medicine, Sapienza University, Roma Paganelli A, Department of Experimental Medicine, Sapienza University, Roma Di Marcotullio L, Department of Experimental Medicine, Sapienza University, Roma Caffarelli E, Institute of Molecular Biology and Pathology, Consiglio Nazionale delle Ricerche, Sapienza University, Roma Screpanti I, Department of Experimental Medicine, Sapienza University, Roma Bozzoni I,Department of Genetics and Molecular Biology, Sapienza University, Roma; Institute of Molecular Biology and Pathology, Consiglio Nazionale delle Ricerche, Sapienza University, Roma Gulino A, Department of Experimental Medicine, Sapienza University, Roma; Neuromed Institute, Pozzilli, Italy (literal)
Titolo
  • Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells (literal)
Abstract
  • MicroRNAs (miRNA) are crucial post-transcriptional regulators of gene expression and control cell differentiation and proliferation. However, little is known about their targeting of specific developmental pathways. Hedgehog (Hh) signalling controls cerebellar granule cell progenitor development and a subversion of this pathway leads to neoplastic transformation into medulloblastoma (MB). Using a miRNA high-throughput profile screening, we identify here a downregulated miRNA signature in human MBs with high Hh signalling. Specifically, we identify miR-125b and miR-326 as suppressors of the pathway activator Smoothened together with miR-324-5p, which also targets the downstream transcription factor Gli1. Downregulation of these miRNAs allows high levels of Hh-dependent gene expression leading to tumour cell proliferation. Interestingly, the downregulation of miR-324-5p is genetically determined by MB-associated deletion of chromosome 17p. We also report that whereas miRNA expression is downregulated in cerebellar neuronal progenitors, it increases alongside differentiation, thereby allowing cell maturation and growth inhibition. These findings identify a novel regulatory circuitry of the Hh signalling and suggest that misregulation of specific miRNAs, leading to its aberrant activation, sustain cancer development. (literal)
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