MiR-196a exerts its oncogenic effect in glioblastoma multiforme by inhibition of IκBα both in vitro and in vivo

Handle URI:
http://hdl.handle.net/10754/563351
Title:
MiR-196a exerts its oncogenic effect in glioblastoma multiforme by inhibition of IκBα both in vitro and in vivo
Authors:
Yang, Guang; Han, 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 ( 0000-0002-7108-3574 ) ; Ai, Jing; Shi, Changbin; Zhao, Shiguang
Abstract:
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.
KAUST Department:
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division; Computer Science Program; Computational Bioscience Research Center (CBRC); Structural and Functional Bioinformatics Group
Publisher:
Oxford University Press (OUP)
Journal:
Neuro-Oncology
Issue Date:
23-Jan-2014
DOI:
10.1093/neuonc/not307
PubMed ID:
24463357
PubMed Central ID:
PMC3984554
Type:
Article
ISSN:
15228517
Sponsors:
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].
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984554
Appears in Collections:
Articles; Structural and Functional Bioinformatics Group; Computer Science Program; Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorYang, Guangen
dc.contributor.authorHan, Dayongen
dc.contributor.authorChen, Xinen
dc.contributor.authorZhang, Damingen
dc.contributor.authorWang, Luen
dc.contributor.authorShi, Chenen
dc.contributor.authorZhang, Weiguangen
dc.contributor.authorLi, Chenguangen
dc.contributor.authorChen, Xiaofengen
dc.contributor.authorLiu, Huaileien
dc.contributor.authorZhang, Dongzhien
dc.contributor.authorKang, Jianhaoen
dc.contributor.authorPeng, Feien
dc.contributor.authorLiu, Ziyien
dc.contributor.authorQi, Jipingen
dc.contributor.authorGao, Xinen
dc.contributor.authorAi, Jingen
dc.contributor.authorShi, Changbinen
dc.contributor.authorZhao, Shiguangen
dc.date.accessioned2015-08-03T11:46:25Zen
dc.date.available2015-08-03T11:46:25Zen
dc.date.issued2014-01-23en
dc.identifier.issn15228517en
dc.identifier.pmid24463357en
dc.identifier.doi10.1093/neuonc/not307en
dc.identifier.urihttp://hdl.handle.net/10754/563351en
dc.description.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: journals.permissions@oup.com.en
dc.description.sponsorshipThis 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].en
dc.publisherOxford University Press (OUP)en
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984554en
dc.subjectApoptosisen
dc.subjectGlioblastomaen
dc.subjectIκBαen
dc.subjectMiR-196aen
dc.subjectTumor growthen
dc.titleMiR-196a exerts its oncogenic effect in glioblastoma multiforme by inhibition of IκBα both in vitro and in vivoen
dc.typeArticleen
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.contributor.departmentComputer Science Programen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentStructural and Functional Bioinformatics Groupen
dc.identifier.journalNeuro-Oncologyen
dc.identifier.pmcidPMC3984554en
dc.contributor.institutionDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Youzheng Street 23, Nangang District, Harbin, Heilongjiang Province 15001, Chinaen
dc.contributor.institutionInstitute of Brain Science, Harbin Medical University, Harbin, Chinaen
dc.contributor.institutionDepartment of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Chinaen
dc.contributor.institutionDepartment of Neurosurgery, New York University Langone Medical Center, School of Medicine, New York, NY, United Statesen
dc.contributor.institutionDepartment of Pathology, First Affiliated Hospital, Harbin Medical University, Harbin, Chinaen
dc.contributor.institutionDepartment of Surgery, University of Chicago, Medical Centerand Pritzker School of Medicine, Chicago, IL, United Statesen
kaust.authorGao, Xinen

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