IDH1R132H decreases the proliferation of U87 glioma cells through upregulation of microRNA-128a

Nie,Quan‑Min; Lin,Ying‑Ying; Yang,Xi; Shen,Lin; Guo,Lie‑Mei; Que,Shuang‑Lin; Li,Xiao‑Xiong; Ge,Jian‑Wei; Wang,Gui‑Song; Xiong,Wen‑Hao; Guo,Pin; Qiu,Yong‑Ming

doi:10.3892/mmr.2015.4241

IDH1R132H decreases the proliferation of U87 glioma cells through upregulation of microRNA-128a

Authors:
- Quan‑Min Nie
- Ying‑Ying Lin
- Xi Yang
- Lin Shen
- Lie‑Mei Guo
- Shuang‑Lin Que
- Xiao‑Xiong Li
- Jian‑Wei Ge
- Gui‑Song Wang
- Wen‑Hao Xiong
- Pin Guo
- Yong‑Ming Qiu
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Affiliations: Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China, Shanghai Institute of Head Trauma, Shanghai 200127, P.R. China, Department of Neurosurgery, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, Fujian 364000, P.R. China, Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
Published online on: August 24, 2015 https://doi.org/10.3892/mmr.2015.4241
Pages: 6695-6701
Copyright: © Nie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mutations in isocitrate dehydrogenase 1 (IDH1) are found in >70% of secondary glioblastomas and lower-grade gliomas (grades II-III). Among the numerous phenotypic differences between IDH1 mutant and wild-type glioma patients, the most salient is an improved survival rate for patients with a mutation. MicroRNAs (miRNAs) are a class of small, non‑coding, single‑stranded RNAs that can negatively regulate gene expression at the post‑transcriptional level, predominantly by binding to the 3'‑untranslated region of their target mRNAs. The dysregulated expression of several miRNAs has been reported to modulate glioma progression; however, it is unclear whether mutations in IDH1 regulate glioma cell proliferation through miRNA dysregulation. In the present study, stable overexpression of IDH1WT or IDH1R132H was established in the U87 glioma cell line. It was found that IDH1R132H decreased cell proliferation of U87 glioma cells by inducing the expression of the miRNA miR‑128a. This process was dependent on the transcription factor hypoxia inducible factor‑1α (HIF‑1α), which binds to a hypoxia response element in the promoter of miR‑128a. Furthermore, miR‑128a negatively regulated the expression of B‑cell‑specific Moloney murine leukemia virus integration site 1 protein (Bmi‑1), which is involved in suppressing cell proliferation. These findings suggest that the IDH1R132H‑HIF‑1α‑miR‑128a‑Bmi‑1 pathway is involved in glioma cell proliferation.

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