Abstract
Purpose
Sevoflurane is a common used inhaled anesthetic that was reported to regulate the progression of multiple cancers. Here, we aimed to investigate the function and regulatory mechanism underlying sevoflurane in glioma cells.
Methods
A172 and U251 cells were treated with different concentrations of sevoflurane. Colony formation, EdU satining and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, and transwell assays were performed to evaluate cell proliferation, apoptosis, migration and invasion, respectively. Circ_VCAN, microRNA-146b-5p (miR-146b-5p) and nuclear factor I B (NFIB) expression levels were assessed by real-time quantitative PCR (RT-qPCR) or western blot. Bioinformatics analysis and dual-luciferase reporter assay were applied to evaluate the correlation between miR-146b-5p and circ_VCAN or NFIB. A xenograft glioma mice model was established to verify the effect of sevoflurane on tumor growth in vivo.
Results
Sevoflurane (Sev) inhibited proliferation, migration, invasion, and elevated apoptosis of A172 and U251 cells. Sevoflurane treatment inhibited the expression of circ_VCAN and NFIB, but elevated the expression of miR-146b-5p in glioma cells. Overexpression of circ_VCAN alleviated the inhibition effects of sevoflurane on the malignant phenotypes of glioma in vitro and in vivo. Besides, miR-146b-5p is a target of circ_VCAN and negatively regulated NFIB expression. Overexpression of miR-146b-5p partly reversed the effects of circ_VCAN in Sev-treated glioma cells. Furthermore, miR-146b-5p deletion enhanced glioma progression in sevoflurane treated glioma cells by targeting NFIB. Moreover, circ_VCAN could upregulate NFIB expression by sponging miR-146b-5p in Sev-treated glioma cells.
Conclusion
Sevoflurane alleviated proliferation, migration and invasion, but enhanced apoptosis of glioma cells through regulating circ_VCAN/miR-146b-5p/NFIB axis.
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Availability of data and materials
The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.
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Funding
This work was supported by Joint project of Medical Science and Technology Research Plan of Henan Province in 2019, project No.: LHGJ20191441.
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Conceptualization and Methodology: Guofang Cheng, Lili Quan and Haibo Qu; Formal analysis and Data curation: Ailing Yang, Jiangge Ye and Yuanbo Feng; Validation and Investigation: Haili Wang, Xiaofang Li, Xiaoli Shi and Hua Pan; Writing—original draft preparation and Writing—review and editing: Haili Wang, Guofang Cheng, Lili Quan, Haibo Qu and Hua Pan; Approval of final manuscript: all authors.
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Highlights
1. Sevoflurane inhibited the malignant phenotypes of glioma in vitro and in vivo.
2. Circ_VCAN upregulated NFIB expression by sponging miR-146b-5p.
3. Sevoflurane repressed glioma progression by regulating circ_VCAN/miR-146b-5p/NFIB axis.
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Wang, H., Cheng, G., Quan, L. et al. Sevoflurane inhibits the malignant phenotypes of glioma through regulating miR-146b-5p/NFIB axis. Metab Brain Dis 37, 1373–1386 (2022). https://doi.org/10.1007/s11011-022-00959-w
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DOI: https://doi.org/10.1007/s11011-022-00959-w