Back to Journals » OncoTargets and Therapy » Volume 10

RNAi for contactin 2 inhibits proliferation of U87-glioma stem cells by downregulating AICD, EGFR, and HES1

Authors Guo Y, Zhang PD, Zhang HT, Zhang P, Xu RX

Received 23 May 2016

Accepted for publication 10 November 2016

Published 13 February 2017 Volume 2017:10 Pages 791—801

DOI https://doi.org/10.2147/OTT.S113390

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Geoffrey Pietersz

Yang Guo,1,* Peidong Zhang,2,3,* Hongtian Zhang,4 Peng Zhang,4 Ruxiang Xu4

1Department of Neurology, 2Department of Cardiovascular Medicine, Zhujiang Hospital, 3Second Clinical Medical College, Southern Medical University, Guangzhou, 4Department of Neurosurgery, Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA, The Bayi Clinical Medical Institute of Southern Medical University, Beijing, People’s Republic of China

*These authors contributed equally to this work

Abstract: Glioblastoma is the most common form of malignant brain tumors and has a poor prognosis. Glioma stem cells (GSCs) are thought to be responsible for the aberrant proliferation and invasion. Targeting the signaling pathways that promote proliferation in GSCs is one of the strategies for glioma treatment. In this study, we found increased expression of contactin 2 (CNTN2) and amyloid β precursor protein (APP) in U87-derived GSCs (U87-GSCs). RNA interference (RNAi) for CNTN2 downregulated the expression of APP intracellular domain (AICD), which is the proteolytic product of APP. Treatment with CNTN2 RNAi inhibited the proliferation of U87-GSCs. CNTN2 RNAi decreased the expression of epidermal growth factor receptor and HES1, which are potential targets of AICD. In summary, inhibition of the CNTN2/APP signaling pathway may repress the proliferation in U87-GSCs via downregulating the expression of HES1 and epidermal growth factor receptor. CNTN2/APP/AICD signaling pathway plays an important role in U87 glial tumorigenesis. Further studies are warranted to elucidate the role of these signaling pathways in other sources of GSCs. Depending on their role in proliferation in other sources of GSCs, members of the CNTN2/APP/AICD signaling pathway may provide novel targets for the development of therapy for glioblastomas.

Keywords: contactin 2, CNTN2, transient axonal glycoprotein-1, TAG1, glioma stem cells

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]