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 journalArticlepeer-review

42 Scopus citations

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
DOIs
StatePublished - Aug 16 2016

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