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

BMC Anesthesiol. 2021 Sep 3;21(1):213. doi: 10.1186/s12871-021-01427-1.

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.

Keywords: Glioma; RORA; Sevoflurane; circRELN; miR-1290.

MeSH terms

  • Anesthetics, Inhalation / pharmacology*
  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Nuclear Receptor Subfamily 1, Group F, Member 1 / metabolism*
  • RNA, Circular / drug effects
  • RNA, Circular / metabolism*
  • Reelin Protein / metabolism
  • Sevoflurane / pharmacology*
  • Up-Regulation

Substances

  • Anesthetics, Inhalation
  • MIRN1290 microRNA, human
  • MicroRNAs
  • Nuclear Receptor Subfamily 1, Group F, Member 1
  • RNA, Circular
  • RORA protein, human
  • Reelin Protein
  • Sevoflurane