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Inhalational Anesthetics Inhibit Neuroglioma Cell Proliferation and Migration via miR-138, -210 and -335
Authors:Masashi Ishikawa  Masae Iwasaki  Hailin Zhao  Junichi Saito  Cong Hu  Qizhe Sun  Atsuhiro Sakamoto  Daqing Ma
Affiliation:1.Department of Anesthesiology and Pain medicine, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan; (M.I.); (A.S.);2.Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London SW10 9NH, UK; (H.Z.); (J.S.); (C.H.); (Q.S.);3.Department of Anesthesiology, Graduate School of Medicine, Hirosaki University, Hirosaki, Aomori 036-8562, Japan
Abstract:Inhalational anesthetics was previously reported to suppress glioma cell malignancy but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNAs upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.
Keywords:microRNA  sevoflurane  desflurane  hypoxia inducible factor-1α    matrix metalloproteinase 9  glioma
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