Johns Hopkins大學醫學院細胞生物學系，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*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?！ね郀柋?OttoHeinrichWarburg)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，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，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，然而谷氨酰胺的代謝調節機制一直不明。
在本研究中，Chi V.Dang帶領的研究小組發現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的可調節基因，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**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。這一研究結果揭示了c-Myc與miRNAs，谷氨酰胺代謝，能量代謝間的調節功能。（創賽新聞中心 canspecsci.com）
推薦原始出處：
Nature 458, 762-765 (9April2009) | 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 ofMedicine,Baltimore, Maryland 21205, USA
11 Laboratory of Toxicology, Faculty of PharmaceuticalSciences,Teikyo University, Sagamiko, Kanagawa 229-0195, Japan
Altered glucose metabolism in cancer cells is termed theWarburgeffect, which describes the propensity of most cancer cellsto takeup glucose avidly and convert it primarily to lactate,despiteavailable oxygen1, 2. Notwithstanding the renewed interestin theWarburg effect, cancer cells also depend on continuedmitochondrialfunction for metabolism, specifically glutaminolysisthatcatabolizes glutamine to generate ATP and lactate3.Glutamine,which is highly transported into proliferating cells4, 5,is amajor source of energy and nitrogen for biosynthesis, and acarbonsubstrate for anabolic processes in cancer cells, buttheregulation of glutamine metabolism is not well understood1, 6.Herewe report that the c-Myc (hereafter referred to as Myc)oncogenictranscription factor, which is known to regulatemicroRNAs7, 8 andstimulate cell proliferation9, transcriptionallyrepresses miR-23aand miR-23b, resulting in greater expression oftheir targetprotein, mitochondrial glutaminase, in human P-493 Blymphoma cellsand PC3 prostate cancer cells. This leads toupregulation ofglutamine catabolism10. Glutaminase convertsglutamine toglutamate, which is further catabolized through thetricarboxylicacid cycle for the production of ATP or serves assubstrate forglutathione synthesis11. The unique means by which Mycregulatesglutaminase uncovers a previously unsuspected link betweenMycregulation of miRNAs, glutamine metabolism, and energy andreactiveoxygen species homeostasis.
