c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism.
c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism.
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DOI：
10.1038/nature07823
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发表时间：
2009-04-09
期刊：
影响因子：
64.8
通讯作者：
Dang, Chi V.
中科院分区：
文献类型：
--
作者：
Gao, Ping;Tchernyshyov, Irina;Chang, Tsung-Cheng;Lee, Yun-Sil;Kita, Kayoko;Ochi, Takafumi;Zeller, Karen I.;De Marzo, Angelo M.;Van Eyk, Jennifer E.;Mendell, Joshua T.;Dang, Chi V.
癌细胞中葡萄糖代谢的改变被称为Warburg效应，它描述了大多数癌细胞贪婪地吸收葡萄糖并将其主要转化为乳酸的倾向，尽管有可用的氧气。尽管对Warburg效应重新产生了兴趣，但癌细胞也依赖于持续的线粒体功能进行代谢，特别是谷氨酰胺分解产生ATP和乳酸。谷氨酰胺被高度运输到增殖细胞中，是生物合成所需能量和氮的主要来源，也是癌细胞合成代谢过程的碳底物，但谷氨酰胺代谢的调控尚不清楚。在这里，我们报道了c-Myc（以下简称Myc）致癌转录因子，已知其调节microrna并刺激细胞增殖，转录抑制miR-23a和miR-23b，导致其靶蛋白线粒体谷氨酰胺酶在人P-493 B淋巴瘤细胞和PC3前列腺癌细胞中的表达增加。这导致谷氨酰胺分解代谢的上调。谷氨酰胺酶将谷氨酰胺转化为谷氨酸，谷氨酸通过三羧酸循环进一步分解代谢产生ATP或作为合成谷胱甘肽的底物。Myc调节谷氨酰胺酶的独特方式揭示了Myc调节mirna、谷氨酰胺代谢、能量和活性氧稳态之间以前未被怀疑的联系。
Altered glucose metabolism in cancer cells is termed the Warburg effect, which describes the propensity of most cancer cells to take up glucose avidly and convert it primarily to lactate, despite available oxygen,. Notwithstanding the renewed interest in the Warburg effect, cancer cells also depend on continued mitochondrial function for metabolism, specifically glutaminolysis that catabolizes glutamine to generate ATP and lactate. Glutamine, which is highly transported into proliferating cells,, is a major source of energy and nitrogen for biosynthesis, and a carbon substrate for anabolic processes in cancer cells, but the regulation of glutamine metabolism is not well understood,. Here we report that the c-Myc (hereafter referred to as Myc) oncogenic transcription factor, which is known to regulate microRNAs,and stimulate cell proliferation, transcriptionally represses miR-23a and miR-23b, resulting in greater expression of their target protein, mitochondrial glutaminase, in human P-493 B lymphoma cells and PC3 prostate cancer cells. This leads to upregulation of glutamine catabolism. Glutaminase converts glutamine to glutamate, which is further catabolized through the tricarboxylic acid cycle for the production of ATP or serves as substrate for glutathione synthesis. The unique means by which Myc regulates glutaminase uncovers a previously unsuspected link between Myc regulation of miRNAs, glutamine metabolism, and energy and reactive oxygen species homeostasis.
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影响因子：
7.4
作者：
YATES, JR;ENG, JK;SCHIELTZ, D
通讯作者：
SCHIELTZ, D
影响因子：
64.8
作者：
O'Donnell, KA;Wentzel, EA;Mendell, JT
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影响因子：
4.2
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通讯作者：
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4.1
作者：
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通讯作者：
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影响因子：
30.8
作者：
Chang, Tsung-Cheng;Yu, Duonan;Mendell, Joshua T.
通讯作者：
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