期刊
AUTOPHAGY
卷 13, 期 3, 页码 554-566出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2016.1269989
关键词
BECN1; lung cancer; microRNA; MTOR; PPP2/PP2A
类别
资金
- Telethon Foundation [GGP14202]
- AIRC [IG2016-18906]
- FISM
- Italian Ministry of Health
- Danish National Supercomputer for Life Science Computerome
- Lundbeck Foundation [R209-2015-3505, R167-2013-16100]
- KBVU [R146-A9471]
- KBVU grant from the Danish Cancer Society [R146-A9364]
- Bjarne Saxhof Foundation
- NovoNordisk Foundation [7559]
- European Union (Horizon MEL-PLEX) [642295]
- Danish National Research Foundation
- Lundbeck Foundation [R209-2015-3505, R167-2013-16100] Funding Source: researchfish
- Novo Nordisk Fonden [NNF13OC0007559] Funding Source: researchfish
- The Danish Cancer Society [R146-A9471, R146-A9364] Funding Source: researchfish
Macroautophagy/autophagy is a tightly regulated intracellular catabolic pathway involving the lysosomal degradation of cytoplasmic organelles and proteins to be recycled into metabolic precursors. AMBRA1 (autophagy and Beclin 1 regulator 1) has a central role in the autophagy signaling network; it acts upstream of MTORC1-dependent autophagy by stabilizing the kinase ULK1 (unc-51 like autophagy activating kinase 1) and by favoring autophagosome core complex formation. AMBRA1 also regulates the cell cycle by modulating the activity of the phosphatase PPP2/PP2A (protein phosphatase 2) and degradation of MYC. Of note, post-transcriptional regulation mediated by noncoding microRNAs (MIRNAs) contributes significantly to control autophagy. Here we describe a new role for the microRNA MIR7-3HG/MIR-7 as a potent autophagy inhibitor. Indeed, MIR7-3HG targets the 30 untranslated region (UTR) of AMBRA1 mRNA, inducing a decrease of both AMBRA1 mRNA and protein levels, and thus causing a block in autophagy. Furthermore, MIR7-3HG, through AMBRA1 downregulation, prevents MYC dephosphorylation, establishing a positive feedback for its own transcription. These data suggest a new and interesting role of MIR7-3HG as an anti-autophagic MIRNA that may affect oncogenesis through the regulation of the tumor suppressor AMBRA1.
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