miR-126&126* Restored Expressions Play a Tumor Suppressor Role by Directly Regulating ADAM9 and MMP7 in Melanoma. (Articolo in rivista)

Type
Label
  • miR-126&126* Restored Expressions Play a Tumor Suppressor Role by Directly Regulating ADAM9 and MMP7 in Melanoma. (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1371/journal.pone.0056824. (literal)
Alternative label
  • Felli N, Felicetti F, Lustri AM, Errico MC, Bottero L, Cannistraci A, De Feo A, Petrini M, Pedini F, Biffoni M, Alvino E, Negrini M, Ferracin M, Mattia G, Carè A. PLoS One. 2013;8(2):e56824. doi: 10.1371/journal.pone.0056824. Epub 2013 Feb 21. PMID: 23437250 [PubMed - in process] (2013)
    miR-126&126* Restored Expressions Play a Tumor Suppressor Role by Directly Regulating ADAM9 and MMP7 in Melanoma.
    in PloS one
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Felli N, Felicetti F, Lustri AM, Errico MC, Bottero L, Cannistraci A, De Feo A, Petrini M, Pedini F, Biffoni M, Alvino E, Negrini M, Ferracin M, Mattia G, Carè A. PLoS One. 2013;8(2):e56824. doi: 10.1371/journal.pone.0056824. Epub 2013 Feb 21. PMID: 23437250 [PubMed - in process] (literal)
Pagina inizio
  • E56824 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 8 (literal)
Rivista
Note
  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • SourceDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy. (literal)
Titolo
  • miR-126&126* Restored Expressions Play a Tumor Suppressor Role by Directly Regulating ADAM9 and MMP7 in Melanoma. (literal)
Abstract
  • The abnormal expression of several microRNAs has a causal role in tumorigenesis with either antineoplastic or oncogenic functions. Here we demonstrated that miR-126 and miR-126* play a tumor suppressor role in human melanoma through the direct or indirect repression of several key oncogenic molecules. The expression levels of miR-126&126* were elevated in normal melanocytes and primary melanoma cell lines, whereas they markedly declined in metastatic cells. Indeed, the restored expression of miR-126&126* in two advanced melanoma cell lines was accompanied by a significant reduction of proliferation, invasion and chemotaxis in vitro as well as of growth and dissemination in vivo. In accordance, the reverse functional effects were obtained by knocking down miR-126&126* by transfecting antisense LNA oligonucleotides in melanoma cells. Looking for the effectors of these antineoplastic functions, we identified ADAM9 and MMP7, two metalloproteases playing a pivotal role in melanoma progression, as direct targets of miR-126&126*. In addition, as ADAM9 and MMP7 share a role in the proteolytic cleavage of the HB-EGF precursor, we looked for the effectiveness of this regulatory pathway in melanoma, confirming the decrease of HB-EGF activation as a consequence of miR-126&126*-dependent downmodulation of ADAM9 and MMP7. Finally, gene profile analyses showed that miR-126&126* reexpression was sufficient to inactivate other key signaling pathways involved in the oncogenic transformation, as PI3K/AKT and MAPK, and to restore melanogenesis, as indicated by KIT/MITF/TYR induction. In view of this miR-126&126* wide-ranging action, we believe that the replacement of these microRNAs might be considered a promising therapeutic approach. PMID: 23437250 [PubMed - in process] (literal)
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