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Cell Rep. 2016 Aug 16;16(7):1915-28. doi: 10.1016/j.celrep.2016.07.036. Epub 2016 Aug 4.

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

Author information

1
Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
2
Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
3
ITMO University, St. Petersburg 197101, Russia; Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO 63110, USA.
4
Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada.
5
Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO 63110, USA.
6
Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
7
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.

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.

PMID:
27498867
DOI:
10.1016/j.celrep.2016.07.036
[Indexed for MEDLINE]
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