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

Ruggero De Maria Marchiano, Micol Eleonora Fiori, Maria Laura De Angelis, Lidia Villanova, Chiara Barbini

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

15 Citazioni (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.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
Numero di pagine13
RivistaCELL DEATH & DISEASE
Volume9
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • lung cancer
  • mir663

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