Sevoflurane blocks glioma malignant development by upregulating circRELN through circRELN-mediated miR-1290/RORA axis

Abstract

Background Sevoflurane (Sev) has been reported to inhibit cancer development, and sevoflurane treatment in cancers is implicated with the deregulation of specific non-coding RNAs (ncRNAs). This study aimed to investigate the relationship between sevoflurane and circular RNA reelin (circRELN) in glioma. Methods The expression of circRELN, microRNA-1290 (miR-1290) and RAR-related orphan receptor A (RORA) was measured by quantitative real-time PCR (qPCR). Cell proliferative capacity was assessed by cell counting kit-8 (CCK-8) and colony formation assays. Cell apoptosis and cell cycle distribution were monitored by flow cytometry assay. Cell migration was assessed by wound healing assay and transwell assay, and cell invasion was assessed by transwell assay. The protein levels of matrix metalloproteinase-2 (MMP2), MMP9 and RORA were quantified by western blot. Tumor growth in vivo was assessed by Xenograft models. The binding relationship between miR-1290 and circRELN or RORA was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results We found that circRELN expression was declined in glioma tissues and cells, while Sev treatment enhanced circRELN expression. In function, Sev notably inhibited glioma cell proliferation, migration and invasion and promoted apoptosis and cell cycle arrest, while circRELN knockdown reversed these effects. MiR-1290 served as a target of circRELN, and glioma cell malignant phenotypes recovered by circRELN knockdown were partly repressed by miR-1290 deficiency. In addition, RORA was a target of miR-1290, and glioma cell malignant phenotypes promoted by miR-1290 restoration were partly blocked by RORA overexpression. CircRELN regulated RORA expression by targeting miR-1290. In Xenograft models, Sev inhibited tumor growth by upregulating circRELN. Conclusion Sev blocked the progression of glioma by increasing circRELN expression, and circRELN played roles in glioma partly by regulating the miR-1290/RORA network.

Molecular mechanisms of tumour development in glioblastoma: an emerging role for the circadian clock

“…On the other hand, CLOCK positively influenced invasion and EMT 18 , 19 . In contrast, RORα and PER2 were observed to inhibit migration and invasion 26 , 29 , 30 . Notably, REV-ERBα and REV-ERBβ showed opposite effects on GBM cell migration, invasion, and chemotaxis as outlined in Fig.…”

“…The nuclear transport protein CRM1 was also rhythmic and peaked 4 h after BMAL1 105 . Sevoflurane Increased levels of RORα, reduced proliferation, migration, and invasion of T98G and N18 cells and increased their apoptosis 26 . Lectin from Abelmoschus esculentus Downregulated BMAL1 and CLOCK in U87-MG cells and led to decreased proliferation and migration, and increased oxidative stress and apoptosis 20 .…”

“…In contrast, Gwon et al showed that overexpression of BMAL1 in U87-MG cells induced apoptosis 31 . On the other hand, RORα increased apoptosis by inactivation of the TNFα (Tumour Necrosis Factor alpha)/NF-κB axis, and activation of NDRG2 (N-Myc Downstream-Regulated Gene 2) 25 , 27 It was reduced by the circRELN (circular RNA Reelin) /miR-1290 (microRNA-1290) axis in GBM 26 . SHP656 was shown to selectively activate CRY2 and treatment with SHP656 had a negative effect on cell viability.…”

An Insight into miR-1290: An Oncogenic miRNA with Diagnostic Potential

“…MiR-1290 was upregulated in glioma tissues compared with normal brain samples and it suppressed the FBXW7 tumor suppressor [275]. Another study showed that miR-1290 promotes a malignant phenotype of glioma cells by targeting the RORA tumor suppressor [276]. Interestingly, miR-1290 was upregulated in exosomes released by glioma stem cells (GSCs) compared with exosomes from normal neural stem cells (NSCs), and exosomes secreted by GSCs influenced the gene expression in receiving NSCs, including genes with a role in tumorigenesis [277].…”

Effect of Inhalation Anesthetics on Tumor Metastasis

“…54 Moreover, a study has confirmed that sevoflurane can block glioma progression by increasing circRNA reelin (circRELN) expression, and circRELN played a role in glioma partly by regulating the miR-1290/RORA network. 55 Similarly, other circRNA-miRNA axes are involved in sevoflurane-mediated glioma inhibition. For example, has_circ_0012129/miR-761/TGIF2, 56 circ_0002755/miR-628-5p/MAGT1, 57 circ_0000215/miR-1200/NCR3LG1, 58 circ_0079593/miR-633/ROCK1, 59 and so on.…”