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 language | English |
---|---|
Pages (from-to) | 1915-1928 |
Number of pages | 14 |
Journal | Cell Reports |
Volume | 16 |
Issue number | 7 |
Early online date | 4 Aug 2016 |
DOIs | |
Publication status | Published - 16 Aug 2016 |
Fingerprint
Dive into the research topics of 'The miR-17∼92 microRNA Cluster Is a Global Regulator of Tumor Metabolism'. Together they form a unique fingerprint.Profiles
-
Dr Emma E Vincent
- Bristol Medical School (THS) - Senior Lecturer in Molecular Metabolism
- School of Cellular and Molecular Medicine - Research Fellow
- Bristol Population Health Science Institute
- Cancer
Person: Academic , Academic , Member