Sevoflurane impedes the progression of glioma through modulating the circular RNA has_circ_0012129/miR-761/TGIF2 axis.
Weiyi Xu, Rui Xue, Rongmu Xia, W.-W. Liu, J.-W. Zheng, Lixin Tang, L-Y Kang, W. Wang, W.-T. Wei
Abstract
OBJECTIVE: Glioma is a highly aggressive and lethal brain tumor. Anesthetics have been shown to have important effects on the biological characteristics of cancer cells. Nevertheless, the molecular mechanism of anesthetic-mediated glioma cells progression remains unclear. MATERIALS AND METHODS: Sevoflurane (sev) was employed to treat glioma cells. The biological characteristics (viability, colony formation, apoptosis, cell cycle, migration, and invasion) of glioma cells were determined via Cell Counting Kit-8 (CCK-8), cell colony formation, flow cytometry, PI cytometry, or transwell assays. The protein levels of Cell Cycle Dependent Kinase (CDK) 2, CDK4, E-cadherin, N-cadherin, Vimentin, and Transforming Growth Factor Beta (TGFB) induced factor homeobox 2 (TGIF2) were assessed through Western blot analysis. Glucose consumption and lactate production were measured using special commercial kits. The expression of circular RNA has_circ_0012129 (circ_0012129) and miR-761 was detected via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between circ_0012129 or TGIF2 and miR-761 was verified with Dual-Luciferase reporter assay. Sevoflurane-mediated molecular mechanisms have been confirmed via xenograft assay. RESULTS: Sevoflurane suppressed viability, colony formation, cell cycle, migration, and invasion and promoted apoptosis of glioma cells in vitro, and impeded tumor growth in vivo. Circ_0012129 and TGIF2 were downregulated and miR-761 was upregulated in sevoflurane-treated glioma cells. Circ_0012129 elevation abolished sevoflurane-mediated biological characteristics of glioma cells. MiR-761 served as target for circ_0012129 and miR-761 targeted TGIF2. Moreover, both miR-761 overexpression and TGIF2 suppression restored circ_0012129 enhancement-mediated biological characteristics of sevoflurane-treated glioma cells. CONCLUSIONS: Sevoflurane mediated the progression of glioma via regulating the circ_0012129/miR-761/TGIF2 axis.