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The miR-17∼92 microRNA Cluster Is a Global Regulator of Tumor Metabolism

Research output: Contribution to journalArticle

  • Said Izreig
  • Bozena Samborska
  • Radia M Johnson
  • Alexey Sergushichev
  • Eric H Ma
  • Carine Lussier
  • Ekaterina Loginicheva
  • Ariel O Donayo
  • Maya C Poffenberger
  • Selena M Sagan
  • Emma E Vincenthttp://orcid.org/0000-0002-8917-7384
  • Maxim N Artyomov
  • Thomas F Duchaine
  • Russell G Jones
Original languageEnglish
Pages (from-to)1915-1928
Number of pages14
JournalCell Reports
Volume16
Issue number7
Early online date4 Aug 2016
DOIs
DateAccepted/In press - 14 Jul 2016
DateE-pub ahead of print - 4 Aug 2016
DatePublished (current) - 16 Aug 2016

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.

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Cell Press at http://www.sciencedirect.com/science/article/pii/S2211124716309548 . Please refer to any applicable terms of use of the publisher.

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Cell Press at http://www.sciencedirect.com/science/article/pii/S2211124716309548 . Please refer to any applicable terms of use of the publisher.

    Final published version, 2 MB, PDF document

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Cell Press at http://www.sciencedirect.com/science/article/pii/S2211124716309548 . Please refer to any applicable terms of use of the publisher.

    Final published version, 6 MB, PDF document

    Licence: CC BY-NC-ND

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