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 3′ 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.

Capizzi, M., Strappazzon, F., Cianfanelli, V., Papaleo, E., Cecconi, F. (2017). MIR7–3HG, a MYC-dependent modulator of cell proliferation, inhibits autophagy by a regulatory loop involving AMBRA1. AUTOPHAGY, 13(3), 554-566 [10.1080/15548627.2016.1269989].

MIR7–3HG, a MYC-dependent modulator of cell proliferation, inhibits autophagy by a regulatory loop involving AMBRA1

Cianfanelli V.;Papaleo E.;
2017-01-01

Abstract

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 3′ 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.
2017
Capizzi, M., Strappazzon, F., Cianfanelli, V., Papaleo, E., Cecconi, F. (2017). MIR7–3HG, a MYC-dependent modulator of cell proliferation, inhibits autophagy by a regulatory loop involving AMBRA1. AUTOPHAGY, 13(3), 554-566 [10.1080/15548627.2016.1269989].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11590/469161
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