Working Paper Article Version 1 This version is not peer-reviewed

Inhalational Anesthetics Inhibit Neuroglioma Cell Proliferation and Migration via miR-138, -210 and -335

Version 1 : Received: 20 March 2021 / Approved: 23 March 2021 / Online: 23 March 2021 (09:14:01 CET)

A peer-reviewed article of this Preprint also exists.

Ishikawa, M.; Iwasaki, M.; Zhao, H.; Saito, J.; Hu, C.; Sun, Q.; Sakamoto, A.; Ma, D. Inhalational Anesthetics Inhibit Neuroglioma CellProliferation and Migration via miR-138, -210 and -335. Int. J. Mol. Sci. 2021, 22, 4355. Ishikawa, M.; Iwasaki, M.; Zhao, H.; Saito, J.; Hu, C.; Sun, Q.; Sakamoto, A.; Ma, D. Inhalational Anesthetics Inhibit Neuroglioma CellProliferation and Migration via miR-138, -210 and -335. Int. J. Mol. Sci. 2021, 22, 4355.

Journal reference: Int. J. Mol. Sci. 2021, 22, 4355
DOI: 10.3390/ijms22094355

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 hrs. 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 miRNA 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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