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01-02-2013 | Laboratory Investigation

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

Authors: Hirotomo Tanaka, Takashi Sasayama, Kazuhiro Tanaka, Satoshi Nakamizo, Masamitsu Nishihara, Katsu Mizukawa, Masaaki Kohta, Junji Koyama, Shigeru Miyake, Masaaki Taniguchi, Kohkichi Hosoda, Eiji Kohmura

Published in: Journal of Neuro-Oncology | Issue 3/2013

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.

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Title: MicroRNA-183 upregulates HIF-1α by targeting isocitrate dehydrogenase 2 (IDH2) in glioma cells
Authors: Hirotomo Tanaka
Takashi Sasayama
Kazuhiro Tanaka
Satoshi Nakamizo
Masamitsu Nishihara
Katsu Mizukawa
Masaaki Kohta
Junji Koyama
Shigeru Miyake
Masaaki Taniguchi
Kohkichi Hosoda
Eiji Kohmura
Publication date: 01-02-2013
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 3/2013
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-012-1027-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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