MicroRNA associated with prognostic factor in glioma

• 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
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: グリオーマ / マイクロ RNA / マイクロＲＮＡ / miR-183 / マイクロRNA / イソクエン酸脱水素酵素 / 予後

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) Issue: 1 Pages: 65-74
  • 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) Issue: 3 Pages: 273-83
  • 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) Issue: 4 Pages: 445-8
  • 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) Issue: 3 Pages: 299-305
  • DOI: 10.1111/j.1440-1789.2012.01349.x
  • Peer Reviewed
• [Journal Article] De-Repression of PDGFRβ Transcription Promotes Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in Glioblastoma Patients. (2013)
  • Author(s): Akhavan D
  • Journal Title: Cancer Discov Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Supratentorial pure cortical ependymoma (2012)
  • Author(s): Nakamizo S, Sasayama T, Kondoh T
  • Journal Title: J Clin Neurosci Volume: 19(10) Issue: 10 Pages: 1453-1455
  • 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) Issue: 3 Pages: 368-80
  • DOI: 10.1093/neuonc/nor203
  • Peer Reviewed
• [Journal Article] Patterns of failure after multimodal treatments for high-grade glioma: (2012)
  • Author(s): Uehara K
  • Journal Title: Radiat Oncol Volume: 26 Issue: 1 Pages: 104-104
  • DOI: 10.1186/1748-717x-7-104
  • Peer Reviewed
• [Journal Article] Cerebrospinal fluid interleukin-10 is a potentially useful biomarker in immunocompetent primary central nervous system lymphoma (PCNSL) (2012)
  • Author(s): Sasayama T, et al
  • Journal Title: Neuro Oncol Volume: 3 Pages: 368-180
  • Peer Reviewed
• [Journal Article] (2011)
  • Author(s): Nishihara M, Sasayama T, Kudo H, Kohmura E.
  • Journal Title: Kobe J Med Sci Volume: 56(4)
  • Peer Reviewed
• [Journal Article] Morbidity of stereotactic biopsy for intracranial lesions (2011)
  • Author(s): Nishihara M, Sasayama T
  • Journal Title: Kobe J Med Sci Volume: 56
  • NAID: 110009585549
  • 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) Issue: 19 Pages: 2205-18
  • DOI: 10.1101/gad.1972310
  • Peer Reviewed
• [Journal Article] Brain metastasis of undifferentiated sarcoma and response to temozolomide treatment. Case report. (2010)
  • Author(s): Tanaka H, Sasayama T, et al.
  • Journal Title: Neurol Med Chir (Tokyo) Volume: 50 Pages: 689-693
  • NAID: 10026651567
  • Peer Reviewed
• [Journal Article] Xanthogranuloma of the sellar region--case report. (2010)
  • Author(s): Arai A, Sasayama T, et al.
  • Journal Title: Neurol Med Chir(Tokyo) Volume: 50 Pages: 488-491
  • NAID: 10030692242
  • Peer Reviewed
• [Journal Article] The novel VEGF receptor antagonist, VGA1155, reduces edema, decreases infarct and improves neurological function after stroke in rats. (2010)
  • Author(s): Koyama J, Miyake S, Sasayama T
  • Journal Title: Kobe J Med Sci. Volume: 56
  • NAID: 110007667735
  • 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] Regulation of IDH2 and HIF-lalpha by microRNA in malignant glioma (2012)
  • Author(s): Hirotomo Tanaka
  • Organizer: 9th Meeting of Asian Society for Neuro-Oncorogy
  • Place of Presentation: 台北（台湾）
• [Presentation] 頭蓋内び慢性大細胞性Bリンパ腫における髄液中IL-10値とB細胞分化マーカーとの関連性 (2012)
  • Author(s): 篠山隆司
  • Organizer: 第30回日本脳腫瘍病理学会
  • Place of Presentation: 名古屋
• [Presentation] 頭蓋内原発悪性リンパ腫におけるJAK-STAT経路の活発化 (2012)
  • Author(s): 篠山隆司
  • Organizer: 第30回日本脳腫瘍学会学術集会
  • Place of Presentation: 広島
• [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, 他
  • Organizer: 脳神経外科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-10-13
• [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