miR-663 sustains NSCLC by inhibiting mitochondrial outer membrane permeabilization (MOMP) through PUMA/BBC3 and BTG2 article

Micol E. Fiori, Lidia Villanova, Chiara Barbini, Maria Laura De Angelis, Ruggero De Maria

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Treatment of lung cancer is an unmet need as it accounts for the majority of cancer deaths worldwide. The development of new therapies urges the identification of potential targets. MicroRNAs' expression is often deregulated in cancer and their modulation has been proposed as a successful strategy to interfere with tumor cell growth and spread. We recently reported on an unbiased high-content approach to identify miRNAs regulating cell proliferation and tumorigenesis in non-small cell lung cancer (NSCLC). Here we studied the oncogenic role of miR-663 in NSCLC biology and analyzed the therapeutic potential of miR-663 targeting. We found that miR-663 regulates apoptosis by controlling mitochondrial outer membrane permeabilization (MOMP) through the expression of two novel direct targets PUMA/BBC3 and BTG2. Specifically, upon miR-663 knockdown the BH3-only protein PUMA/BBC3 directly activates mitochondrial depolarization and cell death, while BTG2 accumulation further enhances this effect by triggering p53 mitochondrial localization. Moreover, we show that miR-663 depletion is sufficient to elicit cell death in NSCLC cells and to impair tumor growth in vivo.

Original languageEnglish
Article number49
JournalCell Death and Disease
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

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Mitochondrial Membranes
Non-Small Cell Lung Carcinoma
MicroRNAs
Neoplasms
Cell Death
Growth
Lung Neoplasms
Carcinogenesis
Cell Proliferation
Apoptosis
Therapeutics
Proteins

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

miR-663 sustains NSCLC by inhibiting mitochondrial outer membrane permeabilization (MOMP) through PUMA/BBC3 and BTG2 article. / Fiori, Micol E.; Villanova, Lidia; Barbini, Chiara; De Angelis, Maria Laura; De Maria, Ruggero.

In: Cell Death and Disease, Vol. 9, No. 2, 49, 01.02.2018.

Research output: Contribution to journalArticle

Fiori, Micol E. ; Villanova, Lidia ; Barbini, Chiara ; De Angelis, Maria Laura ; De Maria, Ruggero. / miR-663 sustains NSCLC by inhibiting mitochondrial outer membrane permeabilization (MOMP) through PUMA/BBC3 and BTG2 article. In: Cell Death and Disease. 2018 ; Vol. 9, No. 2.
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