IDH1R¹³²H decreases the proliferation of U87 glioma cells through upregulation of microRNA-128a.
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.
Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Quan-Min
QM
Nie
Shanghai Institute of Head Trauma, Shanghai 200127, P.R. China.
Ying-Ying
YY
Lin
Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Xi
X
Yang
Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Lin
L
Shen
Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Lie-Mei
LM
Guo
Department of Neurosurgery, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, Fujian 364000, P.R. China.
Shuang-Lin
SL
Que
Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Xiao-Xiong
XX
Li
Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Jian-Wei
JW
Ge
Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Gui-Song
GS
Wang
Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Wen-Hao
WH
Xiong
Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Pin
P
Guo
Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Yong-Ming
YM
Qiu
D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D017354:Point Mutation; D015854:Up-Regulation
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C545189:MIRN128 microRNA, human; D035683:MicroRNAs; D007521:Isocitrate Dehydrogenase