title: The miR-17∼92 microRNA Cluster Is a Global Regulator of Tumor Metabolism.
abstract: A central hallmark of cancer cells is the reprogramming of cellular metabolism to meet the bioenergetic and biosynthetic demands of malignant growth. Here, we report that the miR-17∼92 microRNA (miRNA) cluster is an oncogenic driver of tumor metabolic reprogramming. Loss of miR-17∼92 in Myc(+) tumor cells leads to a global decrease in tumor cell metabolism, affecting both glycolytic and mitochondrial metabolism, whereas increased miR-17∼92 expression is sufficient to drive increased nutrient usage by tumor cells. We mapped the metabolic control element of miR-17∼92 to the miR-17 seed family, which influences cellular metabolism and mammalian target of rapamycin complex 1 (mTORC1) signaling through negative regulation of the LKB1 tumor suppressor. miR-17-dependent tuning of LKB1 levels regulates both the metabolic potential of Myc(+) lymphomas and tumor growth in vivo. Our results establish metabolic reprogramming as a central function of the oncogenic miR-17∼92 miRNA cluster that drives the progression of MYC-dependent tumors.
authors: Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
authors: Said
authors: S
authors: Izreig
authors: Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
authors: Bozena
authors: B
authors: Samborska
authors: Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
authors: Radia M
authors: RM
authors: Johnson
authors: ITMO University, St. Petersburg 197101, Russia; Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors: Alexey
authors: A
authors: Sergushichev
authors: Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
authors: Eric H
authors: EH
authors: Ma
authors: Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada.
authors: Carine
authors: C
authors: Lussier
authors: Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors: Ekaterina
authors: E
authors: Loginicheva
authors: Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada.
authors: Ariel O
authors: AO
authors: Donayo
authors: Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
authors: Maya C
authors: MC
authors: Poffenberger
authors: Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
authors: Selena M
authors: SM
authors: Sagan
authors: Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
authors: Emma E
authors: EE
authors: Vincent
authors: Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors: Maxim N
authors: MN
authors: Artyomov
authors: Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada.
authors: Thomas F
authors: TF
authors: Duchaine
authors: Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada. Electronic address: russell.jones@mcgill.ca.
authors: Russell G
authors: RG
authors: Jones
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis / Q000235:genetics; D064593:Heterografts; D006801:Humans; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D010085:Oxidative Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C568997:MIR17HG, human; C489427:MYC protein, human; D035683:MicroRNAs; D046912:Multiprotein Complexes; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D058570:TOR Serine-Threonine Kinases; D000091162:AMP-Activated Protein Kinase Kinases