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

• DOI: 10.1038/s41419-017-0080-x
• Publication Date: 2018-01-19T11:44:34Z
• Authors: Micol E. Fiori; Lidia Villanova; Chiara Barbini; Maria Laura De An...; Ruggero De Maria
• Keywords: Puma

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