The miR-17∼92 microRNA Cluster Is a Global Regulator of Tumor Metabolism
The miR-17∼92 microRNA Cluster Is a Global Regulator of Tumor Metabolism
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DOI：
10.1016/j.celrep.2016.07.036
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发表时间：
2016-08-16
期刊：
影响因子：
8.8
通讯作者：
Jones, Russell G.
中科院分区：
文献类型：
--
作者：
Izreig, Said;Samborska, Bozena;Jones, Russell G.
癌细胞的一个主要特征是细胞代谢的重新编程，以满足恶性生长的生物能量和生物合成需求。在这里，我们报告了类似于92microRNA(MiRNA)簇的miR-17是肿瘤代谢重编程的致癌驱动因素。在Myc+肿瘤细胞中，类似于92的miR-17的丢失导致肿瘤细胞代谢的全球性下降，影响糖酵解和线粒体代谢，而类似于92表达的miR-17的增加足以推动肿瘤细胞增加对营养的利用。我们将miR-17类似于92的代谢控制元件定位到miR-17种子家族，该家族通过对LKB1肿瘤抑制因子的负调控来影响细胞代谢和哺乳动物靶标雷帕霉素复合体1(MTORC1)信号。依赖于MIR-17的LKB1水平的调节既调节了Myc+淋巴瘤的代谢潜力，也调节了体内肿瘤的生长。我们的结果确定代谢重新编程是致癌miR-17的中心功能，类似于驱动MYC依赖肿瘤进展的92miRNA簇。
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 similar to 92 microRNA (miRNA) cluster is an oncogenic driver of tumor metabolic reprogramming. Loss of miR-17 similar to 92 in Myc + tumor cells leads to a global decrease in tumor cell metabolism, affecting both glycolytic and mitochondrial metabolism, whereas increased miR-17 similar to 92 expression is sufficient to drive increased nutrient usage by tumor cells. We mapped the metabolic control element of miR-17 similar to 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 similar to 92 miRNA cluster that drives the progression of MYC-dependent tumors.