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LncRNA OIP5-AS1 Mitigates Bupivacaine-Induced Neurotoxicity in Dorsal Root Ganglion Neurons Through Regulating NFAT5 Expression via Sponging miR-34b

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Abstract

Bupivacaine (BUP), which is widely used in anesthesia, can cause neurotoxicity and neurological abnormalities. This work intended to study the function of long non-coding RNA (lncRNA) OIP5 antisense RNA 1 (OIP5-AS1) in BUP-triggered neurotoxicity. OIP5-AS1, microRNA (miR)-34b, and nuclear factor of activated T cells 5 (NFAT5) levels were examined via real-time quantitative PCR (RT-qPCR). Cell proliferation, caspase-3 activity, and apoptosis were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), caspase-3 activity, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. The regulatory relationships between miR-34b and OIP5-AS1 or NFAT5 were validated via RNA binding protein immunoprecipitation (RIP) and dual-luciferase reporter assays. Our data demonstrated that OIP5-AS1 and NFAT5 levels were downregulated and miR-34b was upregulated upon exposure to BUP. Functional assays implied that the OIP5-AS1 deficiency impeded cell proliferation and enhanced the apoptosis of DRG neurons, while OIP5-AS1 addition reversed these changes. Moreover, OIP5-AS1 could bind to miR-34b and OIP5-AS1 regulated BUP-induced neurotoxicity via miR-34b. Besides, miR-34b could directly interact with NFAT5. Augmentation of miR-34b impeded cell proliferation and expedited the apoptosis and caspase-3 activity, while NFAT5 addition neutralized these impacts. Finally, it was verified that OIP5-AS1 could upregulate NFAT5 through sponging miR-34b. In sum, our results disclosed that OIP5-AS1 ameliorated BUP-caused neurotoxicity via regulating the miR-34b/NFAT5 axis, suggesting that OIP5-AS1 might be a promising therapeutic target for the treatment of BUP-induced neurotoxicity.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author notes

  1. Yina Yin and Min Ma contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Changzhou Maternity and Child Health Care Hospital, Nanjing Medical University, No.16 Dingxiang Road, Changzhou, 213003, Jiangsu, China

    Yina Yin, Junxiao Chang, Yufang Kong & Guoqiang Chu

  2. Department of Anesthesiology, Affiliate Hospital of Nantong University, Nantong, 226001, China

    Min Ma

  3. Department of Health, Changzhou Maternity and Child Health Care Hospital, Nanjing Medical University, No.16 Dingxiang Road, Changzhou, 213003, Jiangsu, China

    Linlin Rui

  4. Department of Science and Education, Changzhou Maternity and Child Health Care Hospital, Nanjing Medical University, No.16 Dingxiang Road, Changzhou, 213003, Jiangsu, China

    Keliang Zhang

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  1. Yina Yin
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Contributions

YY and MM designed and carried out the study. JC, YK, and LR participated in the experiments and statistical analysis. YY, MM, GC, and KZ wrote and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Guoqiang Chu or Keliang Zhang.

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All animal procedures were approved by the Ethics Committee of Nanjing Medical University.

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Yin, Y., Ma, M., Chang, J. et al. LncRNA OIP5-AS1 Mitigates Bupivacaine-Induced Neurotoxicity in Dorsal Root Ganglion Neurons Through Regulating NFAT5 Expression via Sponging miR-34b. Neurotox Res 40, 2253–2263 (2022). https://doi.org/10.1007/s12640-022-00567-7

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  • DOI: https://doi.org/10.1007/s12640-022-00567-7

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