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CircUBE3B High Expression Participates in Sevoflurane-Induced Human Hippocampal Neuron Injury via Targeting miR-326 and Regulating MYD88 Expression

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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.

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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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Ebbesen KK, Hansen TB, Kjems J (2017) Insights into circular RNA biology. RNA Biol 14:1035–1045

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Hu X, Hu X, Huang G (2019) LncRNA MALAT1 is involved in sevoflurane-induced neurotoxicity in developing rats. J Cell Biochem 120:18209–18218

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Panda AC (2018) Circular RNAs act as miRNA sponges. Adv Exp Med Biol 1087:67–79

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei W, Huo B, Shi X (2019) miR-600 inhibits lung cancer via downregulating the expression of METTL3. Cancer Manag Res 11:1177–1187

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

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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.

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Correspondence to Yingfang Yu.

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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

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