Johns Hopkins大學醫(yī)學院細胞生物學系,，腫瘤學系,，病理系,，Mckusick-Nathans遺傳學研究所等處的研究人員對癌細胞瓦氏效應的研究又取得新的進展,，相關研究成果刊登在最新一期的Nature雜志上,，文章標題為：c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism。
瓦氏效應(Warburg effect),，指奧托·海因里希·瓦爾堡(Otto Heinrich Warburg)所提出的理論,，認為癌細胞的生長速度遠大于正常細胞的原因來自于能量的來源差別。癌細胞會偏向使用糖解作用取代一般正常細胞的有氧循環(huán),，所以癌細胞使用粒線體的方式與正常細胞就會有所不同,。這樣的現象也引起研究者的好奇，是否能借由導引細胞恢復正常有氧循環(huán),，切斷癌細胞的能量供應來阻止癌細胞生長,，所以粒線體以及調控有氧循環(huán)與糖解作用間的過程也一直是癌癥研究的重要問題。
在癌細胞的代謝過程中,，谷氨酰胺的同系物是代謝產生ATP和乳酸的重要組份,，大量的谷氨酰胺會被運輸到癌細胞中促進癌細胞增殖促進生物合成促進碳循環(huán)，然而谷氨酰胺的代謝調節(jié)機制一直不明,。
在本研究中,，Chi V.Dang帶領的研究小組發(fā)現c-Myc原癌基因是促進癌細胞谷氨酰胺代謝的主要轉錄因子。c-Myc基因是myc基因家族的重要成員之一,，c-Myc基因既是一種可易位基因,，又是一種多種物質調節(jié)的可調節(jié)基因，也是一種可使細胞無限增殖,，獲永生化功能,，促進細胞分裂的基因，myc基因參予細胞凋零,，c-mMc基因與多種腫瘤發(fā)生發(fā)展有關,。
C-myc主要通過抑制miR-23a/b來 谷氨酰胺酶的表達以及增強谷氨酰胺的代謝循環(huán)。這一研究結果揭示了c-Myc與miRNAs,，谷氨酰胺代謝,，能量代謝間的調節(jié)功能。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
