MiR-196a exerts its oncogenic effect in glioblastoma multiforme by inhibition of IκBα both in vitro and in vivo
Type
ArticleAuthors
Yang, GuangHan, Dayong
Chen, Xin
Zhang, Daming
Wang, Lu
Shi, Chen
Zhang, Weiguang
Li, Chenguang
Chen, Xiaofeng
Liu, Huailei
Zhang, Dongzhi
Kang, Jianhao
Peng, Fei
Liu, Ziyi
Qi, Jiping
Gao, Xin

Ai, Jing
Shi, Changbin
Zhao, Shiguang
KAUST Department
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) DivisionComputer Science Program
Computational Bioscience Research Center (CBRC)
Structural and Functional Bioinformatics Group
Date
2014-01-23Online Publication Date
2014-01-23Print Publication Date
2014-05Permanent link to this record
http://hdl.handle.net/10754/563351
Metadata
Show full item recordAbstract
BackgroundRecent studies have revealed that miR-196a is upregulated in glioblastoma multiforme (GBM) and that it correlates with the clinical outcome of patients with GBM. However, its potential regulatory mechanisms in GBM have never been reported.MethodsWe used quantitative real-time PCR to assess miR-196a expression levels in 132 GBM specimens in a single institution. Oncogenic capability of miR-196a was detected by apoptosis and proliferation assays in U87MG and T98G cells. Immunohistochemistry was used to determine the expression of IκBα in GBM tissues, and a luciferase reporter assay was carried out to confirm whether IκBα is a direct target of miR-196a. In vivo, xenograft tumors were examined for an antiglioma effect of miR-196a inhibitors.ResultsWe present for the first time evidence that miR-196a could directly interact with IκBα 3′-UTR to suppress IκBα expression and subsequently promote activation of NF-κB, consequently promoting proliferation of and suppressing apoptosis in GBM cells both in vitro and in vivo. Our study confirmed that miR-196a was upregulated in GBM specimens and that high levels of miR-196a were significantly correlated with poor outcome in a large cohort of GBM patients. Our data from human tumor xenografts in nude mice treated with miR-196 inhibitors demonstrated that inhibition of miR-196a could ameliorate tumor growth in vivo.ConclusionsMiR-196a exerts its oncogenic effect in GBM by inhibiting IκBα both in vitro and in vivo. Our findings provide new insights into the pathogenesis of GBM and indicate that miR-196a may predict clinical outcome of GBM patients and serve as a new therapeutic target for GBM. © 2014 © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.Citation
Yang, G., Han, D., Chen, X., Zhang, D., Wang, L., Shi, C., … Zhao, S. (2014). MiR-196a exerts its oncogenic effect in glioblastoma multiforme by inhibition of IκBα both in vitro and in vivo. Neuro-Oncology, 16(5), 652–661. doi:10.1093/neuonc/not307Sponsors
This work was supported by National Natural Science Foundations of China [81302178; 81272788]; Natural Science Foundations of Heilongjiang [QC2013C096]; the Fund of the First Affiliated Hospital of Harbin Medical University [2013B01].Publisher
Oxford University Press (OUP)Journal
Neuro-OncologyPubMed ID
24463357PubMed Central ID
PMC3984554Additional Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984554ae974a485f413a2113503eed53cd6c53
10.1093/neuonc/not307
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