microRNA regulates mTORC2 activity in glioma cells

2013 Fiscal Year Final Research Report

• Project/Area Number: 24791501
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cerebral neurosurgery
• Research Institution: Kobe University
• Principal Investigator: TANAKA Kazuhiro 神戸大学, 医学(系)研究科(研究院), 助教 (70467661)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: グリオーマ / mTORC2 / microRNA / がん代謝 / グルタミン

Research Abstract

mTOR signaling is frequently deregulated in cancer including malignant gliomas. We analyzed if a specific microRNA(miR) controls the expression of Rictor, a main component of mTOR Complex 2. Unfortunately, over-expression of miR-137 or 218 mimic in U87 and U251 glioma cells didn't affect the level of Rictor.
Although the PI3K/mTOR pathway is a master regulator of aerobic glycolysis and cellular biosynthesis, the effect of modulating mTOR activity on other metabolic processes, such as glutamine metabolism is not well understood. Metabolic profiling using gas chromatography and mass spectroscopy (GC/MS) and gene expression analysis of key enzymes for glycolysis and glutaminolysis using RT-PCR methods demonstrated the mTOR-targeted treatments (rapamycin or PP242) regulated glycolysis and stimulated glutamine utilization to elicit a switch in the pathways used to deliver glutamine carbon to the tricarboxylic acid (TCA) cycle.

Research Products

• [Journal Article] mTOR Complex 2 Controls Glycolytic Metabolism in Glioblastoma through FoxO Acetylation and Upregulation of c-Myc (2013)
  • Author(s): Masui K, Tanaka K, Akhavan D, Babic I, Gini B, Matsutani T, Iwanami A, Liu F, Villa GR, Gu Y, Campos C, Zhu S, Yang H, Yong WH, Cloughesy TF, Mellinghoff IK, Cavenee WK, Shaw RJ, Mischel PS
  • Journal Title: CellMetab Volume: 18(5) Pages: 726-39
  • DOI: 10.1016/j.cmet.2013.09.013
  • Peer Reviewed
• [Journal Article] EGFR Mutation-Induced Alternative Splicing of Max Contributes to Growth of Glycolytic Tumors in Brain Cancer (2013)
  • Author(s): Babic I, Anderson ES, Tanaka K, Guo D, Masui K, Li B, Zhu S, Gu Y, Villa GR, Akhavan D, Nathanson D, Gini B, Mareninov S, Li R, Camacho CE, Kurdistani SK, Eskin A, Nelson SF, Yong WH, Cavenee WK, Cloughesy TF, Christofk HR, Black DL, Mischel PS
  • Journal Title: CellMetab Volume: 17(6) Pages: 1000-8
  • DOI: 10.1016/j.cmet.2013.04.013
  • Peer Reviewed
• [Journal Article] GC/MS-based metabolomic analysis of cerebrospinal fluid (CSF) from glioma patients (2013)
  • Author(s): Nakamizo S, Sasayama T, Shinohara M, Irino Y, Nishiumi S, Nishihara M, Tanaka H, Tanaka K, Mizukawa K, Itoh T, Taniguchi M, Hosoda K, Yoshida M, Kohmura E
  • Journal Title: J Neurooncol Volume: 113(1) Pages: 65-74
  • DOI: 10.1007/s11060-013-1090-x
  • Peer Reviewed
• [Journal Article] MicroRNA-183 upregulates HIF-1α by targeting isocitrate dehydrogenase 2 (IDH2) in glioma cells (2013)
  • Author(s): Tanaka H, Sasayama T, Tanaka K, Nakamizo S, Nishihara M, Mizukawa K, Kohta M, Koyama J, Miyake S, Taniguchi M, Hosoda K, Kohmura E
  • Journal Title: J Neurooncol. Volume: 111(3) Pages: 273-83
  • DOI: 10.1007/s11060-012-1027-9
  • Peer Reviewed
• [Presentation] 天幕上low grade glioma 患者の予後規定因子について (2013)
  • Author(s): 田中一寛, 篠山隆司, 西原賢在, 水川克, 甲村英二
  • Organizer: 第72回日本脳神経外科学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20131016-18
• [Presentation] Surgical management of cerebral low-grade gliomas (2013)
  • Author(s): Tanaka K, Sasayama T, Takata K, Mizukawa K, Kohmura E
  • Organizer: The 10th Annual Meeting of Asian Society for Neuro-Oncology
  • Place of Presentation: Mumbai, India
  • Year and Date: 20130321-24
• [Presentation] EGFレセプターの恒常的活性化によるmTORC2-NF-・B 経路の制御 (2012)
  • Author(s): 田中一寛, Paul S. Mischel, 甲村英二
  • Organizer: 第30回日本脳腫瘍学会学術集会
  • Place of Presentation: 広島
  • Year and Date: 20121125-27
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/neuro/TOP2.html