@article{446fdef63f06412a930488d12e50c8dd,
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.",
author = "Said Izreig and Bozena Samborska and Johnson, {Radia M.} and Alexey Sergushichev and Ma, {Eric H.} and Carine Lussier and Ekaterina Loginicheva and Donayo, {Ariel O.} and Poffenberger, {Maya C.} and Sagan, {Selena M.} and Vincent, {Emma E.} and Artyomov, {Maxim N.} and Duchaine, {Thomas F.} and Jones, {Russell G.}",
note = "Funding Information: We thank members of R.G.J.{\textquoteright}s laboratory for discussion of the manuscript, and Drs. Andrea Ventura, Ping Mu, Jerry Pelletier, Nathalie Johnson, and Peiqing Sun for their gift of reagents. We acknowledge technical assistance from the McGill/GCRC Metabolomics and Flow Cytometry core facilities, and the Centre for Applied Genomics at the Hospital for Sick Children. The GCRC Metabolomics Core Facility is supported by grants from the Canadian Foundation for Innovation (CFI), Canadian Institutes of Health Research (CIHR), and Terry Fox Research Institute (TFRI). We acknowledge salary support from the McGill Integrated Cancer Research Training Program (to E.H.M. and S.I.), the Cole Foundation (to S.I.), the Fonds de la Recherche du Qu{\'e}bec – Sant{\'e} (FRQS, to E.H.M., S.I., and T.F.D.), and the CIHR (to R.G.J.). This research has been supported by grants from the CIHR (MOP-136915 to S.M.S., MOP-123352 to T.F.D., and MOP-93799 to R.G.J.) and Terry Fox Research Institute (TFRI-239585 to R.G.J.). This work is dedicated to the memory of Rosalind Goodman. Publisher Copyright: {\textcopyright} 2016 The Author(s)",
year = "2016",
month = aug,
day = "16",
doi = "10.1016/j.celrep.2016.07.036",
language = "English",
volume = "16",
pages = "1915--1928",
journal = "Cell Reports",
issn = "2211-1247",
number = "7",
}