Abstract
The clinical application of Sevoflurane (Sevo) brings about non-negligible neuron injury, leading to postoperative cognitive dysfunction (POCD). However, related pathogenesis is complex and not fully established. We aimed to disclose the role of circRNA UBE3B (circUBE3B) in neuron injury induced by Sevo. Cell viability and apoptosis were determined by CCK-8 and flow cytometry experiments. Inflammation production was monitored by ELISA. The expression of circUBE3B, miR-326, and myeloid differentiation factor 88 (MYD88) mRNA was assessed by quantitative real-time PCR (qPCR). Apoptosis-associated markers and MYD88 protein were quantified by western blot. The putative binding site between miR-326 and circUBE3B or MYD88 was verified by a dual-luciferase reporter experiment, and their binding was validated by a pull-down assay. Sevo treatment weakened cell viability and promoted cell apoptosis and inflammatory response. CircUBE3B expression was elevated in Sevo-treated neurons. Sevo-induced neuron injury was alleviated by circUBE3B downregulation but aggravated by circUBE3B overexpression. MiR-326 was targeted by circUBE3B, and miR-326 inhibition recovered neuron injury that was repressed by circUBE3B absence in Sevo-treated neurons. MiR-326 interacted with MYD88. MiR-326 enrichment attenuated Sevo-induced neuron injury, while these effects were reversed by MYD88 overexpression. CircUBE3B dysregulation was involved in Sevo-induced human hippocampal neuron injury via targeting the miR-326/MYD88 network.
Similar content being viewed by others
Availability of Data and Materials
Not applicable.
References
Ala U (2021) Competing endogenous RNAs and cancer: how coding and non-coding molecules cross-talk can impinge on disease. Int J Biochem Cell Biol 130:105874
Cao C, Deng F, Hu Y (2020) Dexmedetomidine alleviates postoperative cognitive dysfunction through circular RNA in aged rats. 3 Biotech 10:176
Chen J, Xia D, Xu M, Su R, Lin W, Guo D et al (2020a) Expression and significance of MyD88 in patients with gastric cardia cancer in a high-incidence area of China. Front Oncol 10:559
Chen X, Yao Z, Peng X, Wu L, Wu H, Ou Y et al (2020b) Eupafolin alleviates cerebral ischemia/reperfusion injury in rats via blocking the TLR4/NFkappaB signaling pathway. Mol Med Rep 22:5135–5144
Chen Y, Zhang P, Lin X, Zhang H, Miao J, Zhou Y et al (2020c) Mitophagy impairment is involved in sevoflurane-induced cognitive dysfunction in aged rats. Aging (albany NY) 12:17235–17256
Dong W, Dai ZH, Liu FC, Guo XG, Ge CM, Ding J et al (2019) The RNA-binding protein RBM3 promotes cell proliferation in hepatocellular carcinoma by regulating circular RNA SCD-circRNA 2 production. EBioMedicine 45:155–167
Ebbesen KK, Hansen TB, Kjems J (2017) Insights into circular RNA biology. RNA Biol 14:1035–1045
Fang F, Xue Z, Cang J (2012) Sevoflurane exposure in 7-day-old rats affects neurogenesis, neurodegeneration and neurocognitive function. Neurosci Bull 28:499–508
Fang S, Pan J, Zhou C, Tian H, He J, Shen W et al (2019) Circular RNAs serve as novel biomarkers and therapeutic targets in cancers. Curr Gene Ther 19:125–133
Gao R, Chen C, Zhao Q, Li M, Wang Q, Zhou L et al (2020a) Identification of the potential key circular RNAs in elderly patients with postoperative cognitive dysfunction. Front Aging Neurosci 12:165
Gao Y, Ma L, Han T, Wang M, Zhang D, Wang Y (2020b) Protective role of protocatechuic acid in sevoflurane-induced neuron apoptosis, inflammation and oxidative stress in mice. Restor Neurol Neurosci 38:323–331
Guo XQ, Cao YL, Zhao L, Zhang X, Yan ZR, Chen WM (2018) p38 mitogen-activated protein kinase gene silencing rescues rat hippocampal neurons from ketamine-induced apoptosis: an in vitro study. Int J Mol Med 42:1401–1410
He J, Zhao H, Liu X, Wang D, Wang Y, Ai Y et al (2020a) Sevoflurane suppresses cell viability and invasion and promotes cell apoptosis in colon cancer by modulating exosomemediated circHMGCS1 via the miR34a5p/SGPP1 axis. Oncol Rep 44:2429–2442
He B, Chen W, Zeng J, Tong W, Zheng P (2020b) MicroRNA-326 decreases tau phosphorylation and neuron apoptosis through inhibition of the JNK signaling pathway by targeting VAV1 in Alzheimer’s disease. J Cell Physiol 235:480–493
Hu X, Hu X, Huang G (2019) LncRNA MALAT1 is involved in sevoflurane-induced neurotoxicity in developing rats. J Cell Biochem 120:18209–18218
Huang X, Ying J, Yang D, Fang P, Wang X, Zhou B et al (2021) The mechanisms of sevoflurane-induced neuroinflammation. Front Aging Neurosci 13:717745
Li W, Ling HP, You WC, Ji XJ, Tang Y, Zhao JB et al (2013) Recombinant high-mobility group box 1 protein (HMGB-1) promotes myeloid differentiation primary response protein 88 (Myd88) upregulation in mouse primary cortical neurons. Neurol Sci 34:847–853
Li Y, Liu L, Tian Y, Zhang J (2019) Rapamycin improves sevofluraneinduced cognitive dysfunction in aged rats by mediating autophagy through the TLR4/MyD88/NFkappaB signaling pathway. Mol Med Rep 20:3085–3094
Li H, Xia T, Guan Y, Yu Y (2020) Sevoflurane regulates glioma progression by Circ_0002755/miR-628-5p/MAGT1 Axis. Cancer Manag Res 12:5085–5098
Liao Z, Huang Z, Li J, Li H, Miao L, Liu Y et al (2021) Regulation of CRMP2 by Cdk5 and GSK-3beta participates in sevoflurane-induced dendritic development abnormalities and cognitive dysfunction in developing rats. Toxicol Lett 341:68–79
Liu XJ, Liu T, Chen G, Wang B, Yu XL, Yin C et al (2016) TLR signaling adaptor protein MyD88 in primary sensory neurons contributes to persistent inflammatory and neuropathic pain and neuroinflammation. Sci Rep 6:28188
Liu F, Wang Z, Qiu Y, Wei M, Li C, Xie Y et al (2017) Suppression of MyD88-dependent signaling alleviates neuropathic pain induced by peripheral nerve injury in the rat. J Neuroinflammation 14:70
Lv X, Yan J, Jiang J, Zhou X, Lu Y, Jiang H (2017) MicroRNA-27a-3p suppression of peroxisome proliferator-activated receptor-gamma contributes to cognitive impairments resulting from sevoflurane treatment. J Neurochem 143:306–319
Ma R, Wang X, Peng P, Xiong J, Dong H, Wang L et al (2016) Alpha-Lipoic acid inhibits sevoflurane-induced neuronal apoptosis through PI3K/Akt signalling pathway. Cell Biochem Funct 34:42–47
Panda AC (2018) Circular RNAs act as miRNA sponges. Adv Exp Med Biol 1087:67–79
Singh T, Beatty A, Peterson JR (2022) The AMPK-related kinase NUAK2 suppresses glutathione peroxidase 4 expression and promotes ferroptotic cell death in breast cancer cells. Cell Death Discov 8:253
Su G, Yan Z, Deng M (2020) Sevoflurane inhibits proliferation, invasion, but enhances apoptosis of lung cancer cells by Wnt/beta-catenin signaling via regulating lncRNA PCAT6/miR-326 Axis. Open Life Sci 15:159–172
Sun XH, Song MF, Song HD, Wang YW, Luo MJ, Yin LM (2019) miR155 mediates inflammatory injury of hippocampal neuronal cells via the activation of microglia. Mol Med Rep 19:2627–2635
Sun W, Zhao J, Li C (2020) Dexmedetomidine provides protection against hippocampal neuron apoptosis and cognitive impairment in mice with Alzheimer’s disease by mediating the miR-129/YAP1/JAG1 Axis. Mol Neurobiol 57:5044–5055
Tang X, Zhao Y, Zhou Z, Yan J, Zhou B, Chi X et al (2020) Resveratrol mitigates sevoflurane-induced neurotoxicity by the SIRT1-dependent regulation of BDNF expression in developing mice. Oxid Med Cell Longev 2020:9018624
Tian Y, Guo S, Wu X, Ma L, Zhao X (2015) Minocycline alleviates sevoflurane-induced cognitive impairment in aged rats. Cell Mol Neurobiol 35:585–594
Wang L, Zheng M, Wu S, Niu Z (2018) MicroRNA-188-3p is involved in sevoflurane anesthesia-induced neuroapoptosis by targeting MDM2. Mol Med Rep 17:4229–4236
Wang CM, Chen WC, Zhang Y, Lin S, He HF (2021) Update on the mechanism and treatment of sevoflurane-induced postoperative cognitive dysfunction. Front Aging Neurosci 13:702231
Wei W, Huo B, Shi X (2019) miR-600 inhibits lung cancer via downregulating the expression of METTL3. Cancer Manag Res 11:1177–1187
Xu R, Zhu Y, Jia J, Li WX, Lu Y (2021) RIPK1/RIPK3-mediated necroptosis is involved in sevoflurane-induced neonatal neurotoxicity in the rat hippocampus. Cell Mol Neurobiol
Zhang X, Zhou Y, Xu M, Chen G (2016a) Autophagy is involved in the sevoflurane anesthesia-induced cognitive dysfunction of aged rats. PLoS ONE 11:e0153505
Zhang HS, Li H, Zhang DD, Yan HY, Zhang ZH, Zhou CH et al (2016b) Inhibition of myeloid differentiation factor 88(MyD88) by ST2825 provides neuroprotection after experimental traumatic brain injury in mice. Brain Res 1643:130–139
Zhang Q, Huang XM, Liao JX, Dong YK, Zhu JL, He CC et al (2021) LncRNA HOTAIR promotes neuronal damage through facilitating NLRP3 mediated-pyroptosis activation in Parkinson’s disease via regulation of miR-326/ELAVL1 Axis. Cell Mol Neurobiol 41:1773–1786
Zhao Y, Ai Y (2020) Overexpression of lncRNA Gm15621 alleviates apoptosis and inflammation response resulting from sevoflurane treatment through inhibiting miR-133a/Sox4. J Cell Physiol 235:957–965
Zheng X, Chen L, Zhou Y, Wang Q, Zheng Z, Xu B et al (2019) A novel protein encoded by a circular RNA circPPP1R12A promotes tumor pathogenesis and metastasis of colon cancer via Hippo-YAP signaling. Mol Cancer 18:47
Zhou H, Li F, Ye W, Wang M, Zhou X, Feng J et al (2020) Correlation between plasma CircRNA-089763 and postoperative cognitive dysfunction in elderly patients undergoing non-cardiac surgery. Front Behav Neurosci 14:587715
Zhu G, Tao L, Wang R, Xue Y, Wang X, Yang S et al (2017) Endoplasmic reticulum stress mediates distinct impacts of sevoflurane on different subfields of immature hippocampus. J Neurochem 142:272–285
Author information
Authors and Affiliations
Contributions
Xinye Qian designed and performed the research; Shanshan Zheng and Yingfang Yu analyzed the data; Xinye Qian wrote the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics Approval and Consent to Participate
Not applicable.
Consent for Publication
Not applicable.
Competing Interests
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Qian, X., Zheng, S. & Yu, Y. CircUBE3B High Expression Participates in Sevoflurane-Induced Human Hippocampal Neuron Injury via Targeting miR-326 and Regulating MYD88 Expression. Neurotox Res 41, 16–28 (2023). https://doi.org/10.1007/s12640-022-00617-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12640-022-00617-0