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

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 Vincent, Maxim N Artyomov, Thomas F Duchaine, Russell G Jones

Research output: Contribution to journalArticle (Academic Journal)peer-review

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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.

Original languageEnglish
Pages (from-to)1915-1928
Number of pages14
JournalCell Reports
Volume16
Issue number7
Early online date4 Aug 2016
DOIs
Publication statusPublished - 16 Aug 2016

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