MiR-196a exerts its oncogenic effect in glioblastoma multiforme by inhibition of IκBα both in vitro and in vivo
KAUST DepartmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Computer Science Program
Computational Bioscience Research Center (CBRC)
Structural and Functional Bioinformatics Group
Permanent link to this recordhttp://hdl.handle.net/10754/563351
MetadataShow full item record
AbstractBackgroundRecent 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: email@example.com.
SponsorsThis 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].
PublisherOxford University Press (OUP)
PubMed Central IDPMC3984554
- MicroRNA-377 inhibited proliferation and invasion of human glioblastoma cells by directly targeting specificity protein 1.
- Authors: Zhang R, Luo H, Wang S, Chen W, Chen Z, Wang HW, Chen Y, Yang J, Zhang X, Wu W, Zhang SY, Shen S, Dong Q, Zhang Y, Jiang T, Lu D, Zhao S, You Y, Liu N, Wang H
- Issue date: 2014 Nov
- Downregulation of ZMYND11 induced by miR-196a-5p promotes the progression and growth of GBM.
- Authors: Yang JP, Yang JK, Li C, Cui ZQ, Liu HJ, Sun XF, Geng SM, Lu SK, Song J, Guo CY, Jiao BH
- Issue date: 2017 Dec 16
- The miR-92b functions as a potential oncogene by targeting on Smad3 in glioblastomas.
- Authors: Wu ZB, Cai L, Lin SJ, Lu JL, Yao Y, Zhou LF
- Issue date: 2013 Sep 5
- MiR-124 inhibits the growth of glioblastoma through the downregulation of SOS1.
- Authors: Lv Z, Yang L
- Issue date: 2013 Aug
- MicroRNA-210 regulates cell proliferation and apoptosis by targeting regulator of differentiation 1 in glioblastoma cells.
- Authors: Zhang S, Lai N, Liao K, Sun J, Lin Y
- Issue date: 2015