title: MIR7-3HG, a MYC-dependent modulator of cell proliferation, inhibits autophagy by a regulatory loop involving AMBRA1.
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.
authors.affiliation: a Department of Biology , University of Tor Vergata , Rome , Italy.|b IRCCS Fondazione , Santa Lucia, Rome , Italy.
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Capizzi
authors.affiliation: b IRCCS Fondazione , Santa Lucia, Rome , Italy.
authors.forename: Flavie
authors.initials: F
authors.lastname: Strappazzon
authors.affiliation: c Unit of Cell Stress and Survival , Danish Cancer Society Research Center , Copenhagen , Denmark.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cianfanelli
authors.affiliation: d Computational Biology Laboratory, Danish Cancer Society Research Center , Copenhagen , Denmark.
authors.forename: Elena
authors.initials: E
authors.lastname: Papaleo
authors.affiliation: a Department of Biology , University of Tor Vergata , Rome , Italy.|c Unit of Cell Stress and Survival , Danish Cancer Society Research Center , Copenhagen , Denmark.|e Department of Pediatric Hematology and Oncology , IRCCS Bambino Gesù Children's Hospital , Rome , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cecconi
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000072283:A549 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000235:genetics; D001483:Base Sequence; D049109:Cell Proliferation / Q000235:genetics; D003198:Computer Simulation; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C553334:AMBRA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C470507:MIR7-3HG long non-coding RNA, human; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D010768:Phosphoserine
keywords: BECN1; MTOR; PPP2/PP2A; lung cancer; microRNA