Antitumor effect of miR-197 targeting in p53 wild-type lung cancer

Tobias Longin Haas, Ruggero De Maria Marchiano, Micol Eleonora Fiori, M. E. Fiori, C. Barbini, N. Marroncelli, M. Patrizii, M. Biffoni

Risultato della ricerca: Contributo in rivistaArticolo in rivista

64 Citazioni (Scopus)

Abstract

Lung cancer is the leading cause of tumor-related death. The lack of effective treatments urges the development of new therapeutic approaches able to selectively kill cancer cells. The connection between aberrant microRNA (miRNA-miR) expression and tumor progression suggests a new strategy to fight cancer by interfering with miRNA function. In this regard, LNAs (locked nucleic acids) have proven to be very promising candidates for miRNA neutralization. Here, we employed an LNA-based anti-miR library in a functional screening to identify putative oncogenic miRNAs in non-small-cell lung cancer (NSCLC). By screening NIH-H460 and A549 cells, miR-197 was identified as a new functional oncomiR, whose downregulation induces p53-dependent lung cancer cell apoptosis and impairs the capacity to establish tumor xenografts in immunodeficient mice. We further identified the two BH3-only proteins NOXA and BMF as new miR-197 targets responsible for induction of apoptosis in p53 wild-type cells, delineating miR-197 as a key survival factor in NSCLC. Thus, we propose the inhibition of miR-197 as a novel therapeutic approach against lung cancer. © 2014 Macmillan Publishers Limited All rights reserved.
Lingua originaleEnglish
pagine (da-a)774-782
Numero di pagine9
RivistaCell Death and Differentiation
Volume21
DOI
Stato di pubblicazionePubblicato - 2014

Keywords

  • Animals
  • Cell Biology
  • Cell Growth Processes
  • Cell Line, Tumor
  • Female
  • Genomics
  • Humans
  • LNA
  • Lung Neoplasms
  • Mice
  • Mice, Nude
  • MicroRNAs
  • Molecular Biology
  • Molecular Targeted Therapy
  • Oligonucleotides
  • Transfection
  • Tumor Suppressor Protein p53
  • Xenograft Model Antitumor Assays
  • apoptosis
  • lung cancer
  • microRNAs
  • p53

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