First Author | Izreig S | Year | 2016 |
Journal | Cell Rep | Volume | 16 |
Issue | 7 | Pages | 1915-28 |
PubMed ID | 27498867 | Mgi Jnum | J:238963 |
Mgi Id | MGI:5824631 | Doi | 10.1016/j.celrep.2016.07.036 |
Citation | Izreig S, et al. (2016) The miR-17 approximately 92 microRNA Cluster Is a Global Regulator of Tumor Metabolism. Cell Rep 16(7):1915-28 |
abstractText | 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 approximately 92 microRNA (miRNA) cluster is an oncogenic driver of tumor metabolic reprogramming. Loss of miR-17 approximately 92 in Myc(+) tumor cells leads to a global decrease in tumor cell metabolism, affecting both glycolytic and mitochondrial metabolism, whereas increased miR-17 approximately 92 expression is sufficient to drive increased nutrient usage by tumor cells. We mapped the metabolic control element of miR-17 approximately 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 approximately 92 miRNA cluster that drives the progression of MYC-dependent tumors. |