MicroRNA associated with prognostic factor in glioma

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591610
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Kobe University
• Principal Investigator: SASAYAMA Takashi 神戸大学, 医学部附属病院, 講師 (10379399)
• Co-Investigator(Kenkyū-buntansha): NISHIHARA Masamitsu 神戸大学, 医学部, 医学研究員 (20452493)
• Project Period (FY): 2010 – 2012
• Keywords: グリオーマ / マイクロ RNA

Research Abstract

MicroRNAs (miRs) are small, non-coding RNAs that regulate geneexpression and contribute to cell proliferation, differentiation and metabolism. Our previous study revealed the extensive modulation of a set of miRs in malignant glioma. In that study, miR microarray analysis demonstrated the upregulation of microRNA-183 (miR-183) in glioblastomas. Therefore, we examined the expression levels of miR-183 in various types of gliomas and the association of miR-183 with isocitrate dehydrogenase 2 (IDH2), which has complementary sequences to miR-183 in its 3’-untranslated region (3’UTR). In present study, we used real-time PCR analysis to demonstrate that miR-183 is upregulated in the majority of high-grade gliomas and glioma cell lines compared with peripheral, non-tumorous brain tissue. The mRNA and protein expression levels of IDH2 are downregulated via the overexpression of miR-183 mimic RNA in glioma cells. Additionally, IDH2 mRNA expression is upregulated in glioma cells expressing anti-miR-183. We verified that miR-183 directly affects IDH2 mRNA levels in glioma cells using luciferase assays. In malignant glioma specimens, the expression levels of IDH2 were lower in tumors than in the peripheral, non-tumorous brain tissues. HIF-1αlevels were upregulated in glioma cells following transfectionwith miR-183 mimic RNA or IDH2 siRNA. Moreover, vascular endothelial growth factor (VEGF) and glucose transporter 1 (GLUT1), which are downstream molecules of HIF-1α, were upregulated in cells transfected with miR-183 mimic RNA.These results suggest that miR-183 upregulation in malignant gliomas induces HIF-1αexpression by targeting IDH2 and may play a role in glioma biology.

Research Products

• [Journal Article] (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: DOI:10.1007/s11060-013-1090-x.
  • Peer Reviewed
• [Journal Article] (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: DOI:10.1007/s11060-012-1027-9
  • Peer Reviewed
• [Journal Article] (2013)
  • Author(s): Taniguchi M, Nishihara M, Sasayama T, Takahashi Y, Kohmura E
  • Journal Title: Neuropathol Appl Neurobiol Volume: 39(4) Pages: 445-8
  • DOI: DOI:10.1111/nan.12000
  • Peer Reviewed
• [Journal Article] (2013)
  • Author(s): Akhavan D, Pourzia AL, Nourian AA, Williams KJ, Nathanson D, Babic I, Villa GR, Tanaka K, Nael A, Yang H, Dang J, Vinters HV, Yong WH, Flagg M, Tamanoi F, Sasayama T, James CD, Kornblum HI, Cloughesy TF, Cavenee WK, Bensinger SJ, Mischel PS
  • Journal Title: Cancer Discov Volume: 3(5) Pages: 534-547
  • Peer Reviewed
• [Journal Article] (2013)
  • Author(s): Ishii T, Mizukawa K, Sasayama T, Sasaki H, Hayashi S, Nakamizo S, Tanaka H, Tanaka K, Hara S, Hirai C, Itoh T, Kohmura E
  • Journal Title: Neuropathology Volume: 33(3) Pages: 299-305
  • DOI: DOI:10.1111/j.1440-1789.2012.01349.x.
  • Peer Reviewed
• [Journal Article] (2012)
  • Author(s): Nakamizo S, Sasayama T, Kondoh T, Inoue S, Shiomi R, Tanaka H, Nishihara M, Mizukawa K, Uehara K, Usami Y, Kohmura E.
  • Journal Title: J Clin Neurosci Volume: 19(10) Pages: 1453-5
  • DOI: DOI:10.1016/j.jocn.2011.09.039
  • Peer Reviewed
• [Journal Article] (2012)
  • Author(s): Sasayama T, Nakamizo S, Nishihara M, Kawamura A, Tanaka H, Mizukawa K, Miyake S, Taniguchi M, Hosoda K, Kohmura E
  • Journal Title: Neuro Oncol Volume: 14(3) Pages: 368-80
  • DOI: DOI:10.1093/neuonc/nor203
  • Peer Reviewed
• [Journal Article] (2011)
  • Author(s): Nishihara M, Sasayama T, Kudo H, Kohmura E.
  • Journal Title: Kobe J Med Sci Volume: 56(4) Pages: E148-53
  • Peer Reviewed
• [Journal Article] (2010)
  • Author(s): Ozawa T, Brennan CW, Wang L, Squatrito M, Sasayama T, Nakada M, Huse JT, Pedraza A, Utsuki S, Yasui Y, Tandon A, Fomchenko EI, Oka H, Levine RL, Fujii K, Ladanyi M, Holland EC
  • Journal Title: Genes Dev Volume: 24(19) Pages: 2205-18
  • DOI: DOI:10.1101/gad.1972310
  • Peer Reviewed
• [Presentation] Regulation of IDH2 and HIF-1alpha by microRNA in malignant glioma (2012)
  • Author(s): Tanaka H, Sasayama Tet al
  • Organizer: 9thAnnual Meeting of Asian Society for Neuro-Oncology
  • Place of Presentation: Taipei Taiwan
  • Year and Date: 2012-04-21
• [Presentation] 他、悪性グリオーマにおける IDH2 発現とマイクロ RNA による発現制御 (2011)
  • Author(s): 田中宏知、篠山隆司、西原賢在他
  • Organizer: 第12回日本分子脳神経外科学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-10-14
• [Presentation] 悪性グリオーマにおける IDH2 発現とマイクロ RNA による発現制御 (2011)
  • Author(s): 田中宏知、篠山隆司、西原賢在他
  • Organizer: 日本脳神経外科学会第70回学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-10-12