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CircFOXO3 promotes glioblastoma progression by acting as a competing endogenous RNA for NFAT5.
- Source :
-
Neuro-oncology [Neuro Oncol] 2019 Oct 09; Vol. 21 (10), pp. 1284-1296. - Publication Year :
- 2019
-
Abstract
- Background: Circular RNAs (circRNAs), a newly discovered type of endogenous noncoding RNA, have been proposed to mediate the progression of diverse types of tumors. Systematic studies of circRNAs have just begun, and the physiological roles of circRNAs remain largely unknown. Here, we focused on elucidating the potential role and molecular mechanism of circular forkhead box O3 (circFOXO3) in glioblastoma (GBM) progression.<br />Methods: First, we analyzed circFOXO3 alterations in GBM and noncancerous tissues through real-time quantitative reverse transcription PCR (qRT-PCR). Next, we used loss- and gain-of-function approaches to evaluate the effect of circFOXO3 on GBM cell proliferation and invasion. Mechanistically, fluorescent in situ hybridization, RNA pull-down, dual luciferase reporter, and RNA immunoprecipitation assays were performed to confirm the interaction between circFOXO3 and miR-138-5p/miR-432-5p in GBM. An animal model was used to verify the in vitro experimental findings.<br />Results: CircFOXO3 expression was significantly higher in GBM tissues than in noncancerous tissues. GBM cell proliferation and invasion were reduced by circFOXO3 knockdown and enhanced by circFOXO3 overexpression. Further biochemical analysis showed that circFOXO3 exerted its pro-tumorigenic activity by acting as a competing endogenous RNA (ceRNA) to increase expression of nuclear factor of activated T cells 5 (NFAT5) via sponging both miR-138-5p and miR-432-5p. Notably, tumor inhibition by circFOXO3 downregulation could be reversed by miR-138-5p/miR-432-5p inhibitors in GBM cells. Moreover, GBM cells with lower circFOXO3 expression developed less aggressive tumors in vivo.<br />Conclusions: Our data demonstrate that circFOXO3 can exert regulatory functions in GBM and that ceRNA-mediated microRNA sequestration might be a potential strategy for GBM therapy.<br /> (© The Author(s) 2019. 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.)
- Subjects :
- Animals
Brain Neoplasms genetics
DNA, Circular genetics
Disease Progression
Glioblastoma genetics
Heterografts
Humans
Mice
Mice, Nude
MicroRNAs genetics
Transcription Factors metabolism
Brain Neoplasms pathology
Forkhead Box Protein O3 genetics
Gene Expression Regulation, Neoplastic genetics
Glioblastoma pathology
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1523-5866
- Volume :
- 21
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Neuro-oncology
- Publication Type :
- Academic Journal
- Accession number :
- 31504797
- Full Text :
- https://doi.org/10.1093/neuonc/noz128