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

M.E. Fiori, L. Villanova, C. Barbini, M.L. De Angelis, R. De Maria

Research output: Contribution to journalArticlepeer-review


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. © 2018 The Author(s).
Original languageEnglish
JournalCell Death and Disease
Issue number2
Publication statusPublished - 2018


  • BH3 protein
  • BTG2 protein
  • microRNA
  • microRNA 663
  • protein
  • PUMA protein
  • unclassified drug
  • animal experiment
  • animal model
  • apoptosis
  • Article
  • cell death
  • controlled study
  • female
  • human
  • human cell
  • in vivo study
  • membrane depolarization
  • mitochondrial membrane
  • mouse
  • non small cell lung cancer
  • nonhuman
  • outer membrane
  • priority journal
  • protein expression

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