Journal of Neuro-Oncology

, Volume 111, Issue 3, pp 273–283

MicroRNA-183 upregulates HIF-1α by targeting isocitrate dehydrogenase 2 (IDH2) in glioma cells

  • Hirotomo Tanaka
  • Takashi Sasayama
  • Kazuhiro Tanaka
  • Satoshi Nakamizo
  • Masamitsu Nishihara
  • Katsu Mizukawa
  • Masaaki Kohta
  • Junji Koyama
  • Shigeru Miyake
  • Masaaki Taniguchi
  • Kohkichi Hosoda
  • Eiji Kohmura
Laboratory Investigation

DOI: 10.1007/s11060-012-1027-9

Cite this article as:
Tanaka, H., Sasayama, T., Tanaka, K. et al. J Neurooncol (2013) 111: 273. doi:10.1007/s11060-012-1027-9

Abstract

MicroRNAs (miRs) are small, non-coding RNAs that regulate gene expression 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-1α levels were upregulated in glioma cells following transfection with miR-183 mimic RNA or IDH2 siRNA. Moreover, vascular endothelial growth factor and glucose transporter 1, 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-1α expression by targeting IDH2 and may play a role in glioma biology.

Keywords

miR-183IDH2HIF-1αGlioblastoma

Supplementary material

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Supplementary material 1 (TIFF 299 kb)
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Supplementary material 3 (TIFF 100 kb)
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Supplementary material 4 (DOCX 13 kb)

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Hirotomo Tanaka
    • 1
  • Takashi Sasayama
    • 1
  • Kazuhiro Tanaka
    • 1
  • Satoshi Nakamizo
    • 1
  • Masamitsu Nishihara
    • 2
  • Katsu Mizukawa
    • 1
  • Masaaki Kohta
    • 1
  • Junji Koyama
    • 1
  • Shigeru Miyake
    • 1
  • Masaaki Taniguchi
    • 1
  • Kohkichi Hosoda
    • 1
  • Eiji Kohmura
    • 1
  1. 1.Department of NeurosurgeryKobe University Graduate School of MedicineKobeJapan
  2. 2.Department of NeurosurgeryNishi-Kobe Medical CenterKobeJapan