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

M. E. Fiori, C. Barbini, T. L. Haas, N. Marroncelli, M. Patrizii, M. Biffoni, R. De Maria

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)774-782
Number of pages9
JournalCell Death and Differentiation
Volume21
Issue number5
DOIs
Publication statusPublished - 2014

Fingerprint

MicroRNAs
Lung Neoplasms
Neoplasms
Non-Small Cell Lung Carcinoma
Apoptosis
Heterografts
Libraries
Down-Regulation
Therapeutics
Proteins
locked nucleic acid

Keywords

  • apoptosis
  • LNA
  • lung cancer
  • microRNAs
  • p53

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Fiori, M. E., Barbini, C., Haas, T. L., Marroncelli, N., Patrizii, M., Biffoni, M., & De Maria, R. (2014). Antitumor effect of miR-197 targeting in p53 wild-type lung cancer. Cell Death and Differentiation, 21(5), 774-782. https://doi.org/10.1038/cdd.2014.6

Antitumor effect of miR-197 targeting in p53 wild-type lung cancer. / Fiori, M. E.; Barbini, C.; Haas, T. L.; Marroncelli, N.; Patrizii, M.; Biffoni, M.; De Maria, R.

In: Cell Death and Differentiation, Vol. 21, No. 5, 2014, p. 774-782.

Research output: Contribution to journalArticle

Fiori, ME, Barbini, C, Haas, TL, Marroncelli, N, Patrizii, M, Biffoni, M & De Maria, R 2014, 'Antitumor effect of miR-197 targeting in p53 wild-type lung cancer', Cell Death and Differentiation, vol. 21, no. 5, pp. 774-782. https://doi.org/10.1038/cdd.2014.6
Fiori ME, Barbini C, Haas TL, Marroncelli N, Patrizii M, Biffoni M et al. Antitumor effect of miR-197 targeting in p53 wild-type lung cancer. Cell Death and Differentiation. 2014;21(5):774-782. https://doi.org/10.1038/cdd.2014.6
Fiori, M. E. ; Barbini, C. ; Haas, T. L. ; Marroncelli, N. ; Patrizii, M. ; Biffoni, M. ; De Maria, R. / Antitumor effect of miR-197 targeting in p53 wild-type lung cancer. In: Cell Death and Differentiation. 2014 ; Vol. 21, No. 5. pp. 774-782.
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