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

doi:10.1016/j.celrep.2016.07.036

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 journal › Article (Academic Journal) › peer-review

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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	https://doi.org/10.1016/j.celrep.2016.07.036
Publication status	Published - 16 Aug 2016

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10.1016/j.celrep.2016.07.036

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Dr Emma E Vincent
- emma.vincent@bristol.ac.uk
- School of Cellular and Molecular Medicine - Research Fellow
- Bristol Medical School (PHS) - Research Fellow
- Bristol Population Health Science Institute
- Cancer
Person: Academic , Member

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Izreig, S., Samborska, B., Johnson, R. M., Sergushichev, A., Ma, E. H., Lussier, C., Loginicheva, E., Donayo, A. O., Poffenberger, M. C., Sagan, S. M., Vincent, E. E., Artyomov, M. N., Duchaine, T. F., & Jones, R. G. (2016). The miR-17∼92 microRNA Cluster Is a Global Regulator of Tumor Metabolism. Cell Reports, 16(7), 1915-1928. https://doi.org/10.1016/j.celrep.2016.07.036

Izreig, Said ; Samborska, Bozena ; Johnson, Radia M ; Sergushichev, Alexey ; Ma, Eric H ; Lussier, Carine ; Loginicheva, Ekaterina ; Donayo, Ariel O ; Poffenberger, Maya C ; Sagan, Selena M ; Vincent, Emma E ; Artyomov, Maxim N ; Duchaine, Thomas F ; Jones, Russell G. / The miR-17∼92 microRNA Cluster Is a Global Regulator of Tumor Metabolism. In: Cell Reports. 2016 ; Vol. 16, No. 7. pp. 1915-1928.

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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}",

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The miR-17∼92 microRNA Cluster Is a Global Regulator of Tumor Metabolism. / Izreig, Said; Samborska, Bozena; Johnson, Radia M; Sergushichev, Alexey; Ma, Eric H; Lussier, Carine; Loginicheva, Ekaterina; Donayo, Ariel O; Poffenberger, Maya C; Sagan, Selena M; Vincent, Emma E; Artyomov, Maxim N; Duchaine, Thomas F; Jones, Russell G.

In: Cell Reports, Vol. 16, No. 7, 16.08.2016, p. 1915-1928.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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T1 - The miR-17∼92 microRNA Cluster Is a Global Regulator of Tumor Metabolism

AU - Izreig, Said

AU - Samborska, Bozena

AU - Johnson, Radia M

AU - Sergushichev, Alexey

AU - Ma, Eric H

AU - Lussier, Carine

AU - Loginicheva, Ekaterina

AU - Donayo, Ariel O

AU - Poffenberger, Maya C

AU - Sagan, Selena M

AU - Vincent, Emma E

AU - Artyomov, Maxim N

AU - Duchaine, Thomas F

AU - Jones, Russell G

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N2 - 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.

AB - 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.

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DO - 10.1016/j.celrep.2016.07.036

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EP - 1928

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

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ER -

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

Abstract

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Dr Emma E Vincent

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