Johns Hopkins大学医学院细胞生物学系，肿瘤学系，病理系，Mckusick-Nathans遗传学研究所等处的研究人员对癌细胞瓦氏效应的研究又取得新的进展，相关研究成果刊登在最新一期的Nature杂志上，文章标题为：c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism。
瓦氏效应(Warburg effect)，指奥托·海因里希·瓦尔堡(Otto Heinrich Warburg)所提出的理论，认为癌细胞的生长速度远大于正常细胞的原因来自于能量的来源差别。癌细胞会偏向使用糖解作用取代一般正常细胞的有氧循环，所以癌细胞使用粒线体的方式与正常细胞就会有所不同。这样的现象也引起研究者的好奇，是否能借由导引细胞恢复正常有氧循环，切断癌细胞的能量供应来阻止癌细胞生长，所以粒线体以及调控有氧循环与糖解作用间的过程也一直是癌症研究的重要问题。
在癌细胞的代谢过程中，谷氨酰胺的同系物是代谢产生ATP和乳酸的重要组份，大量的谷氨酰胺会被运输到癌细胞中促进癌细胞增殖促进生物合成促进碳循环，然而谷氨酰胺的代谢调节机制一直不明。
在本研究中，Chi V.Dang带领的研究小组发现c-Myc原癌基因是促进癌细胞谷氨酰胺代谢的主要转录因子。c-Myc基因是myc基因家族的重要成员之一，c-Myc基因既是一种可易位基因，又是一种多种物质调节的可调节基因，也是一种可使细胞无限增殖，获永生化功能，促进细胞分裂的基因，myc基因参予细胞凋零，c-mMc基因与多种肿瘤发生发展有关。
C-myc主要通过抑制miR-23a/b来 谷氨酰胺酶的表达以及增强谷氨酰胺的代谢循环。这一研究结果揭示了c-Myc与miRNAs，谷氨酰胺代谢，能量代谢间的调节功能。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 458, 762-765 (9 April 2009) | doi:10.1038/nature07823
c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism
Ping Gao1, Irina Tchernyshyov2, Tsung-Cheng Chang3, Yun-Sil Lee3, Kayoko Kita11, Takafumi Ochi11, Karen I. Zeller1, Angelo M. De Marzo6,7,8, Jennifer E. Van Eyk2,9, Joshua T. Mendell3,4,5 & Chi V. Dang1,3,5,6,7,10
1 Division of Hematology, Department of Medicine,
2 Division of Cardiology, Department of Medicine,
3 McKusick-Nathans Institute of Genetic Medicine,
4 Departments of Pediatrics and,
5 Molecular Biology and Genetics,
6 Departments of Pathology,
7 Oncology,
8 Urology,
9 Biological Chemistry and,
10 Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
11 Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 229-0195, Japan
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 oxygen1, 2. 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 lactate3. Glutamine, which is highly transported into proliferating cells4, 5, 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 understood1, 6. Here we report that the c-Myc (hereafter referred to as Myc) oncogenic transcription factor, which is known to regulate microRNAs7, 8 and stimulate cell proliferation9, 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 catabolism10. 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 synthesis11. 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.
