Effect of miR-132 on bupivacaine-induced neurotoxicity in human neuroblastoma cell line

J Pharmacol Sci. 2019 Mar;139(3):186-192. doi: 10.1016/j.jphs.2019.01.014. Epub 2019 Feb 19.


Background: Local anesthetics (LAs) may generate neurotoxicity in neurons. In the current study, we explored the mechanisms by which microRNA-132 (miR-132) regulated the neurotoxicity of human neuroblastoma cells (SH-SY5Y) induced by bupivacaine (BUP).

Methods: CCK-8, flow cytometry, EdU detection, qRT-PCR and western blotting were used to explore the cell viability, apoptosis and gene expression, respectively.

Results: In this study, we found that 600 μM BUP dramatically inhibited SH-SY5Y cells viability. In addition, BUP induced cell apoptosis and neurotoxicity via increasing active caspase-3 and cleaved PARP1 levels. More importantly, the level of miR-132 was significantly up-regulated in BUP-treated cells, which was significantly reversed by miR-132 inhibitor. In addition, dual-luciferase assay indicated IGF1R was the directly binding target of miR-132 in cells. Our study further indicated that the level of IGF1R was markedly decreased by BUP interference, while miR-132 inhibitor exerted the opposite effect. Furthermore, BUP induced apoptosis and neurotoxicity in SH-SY5Y cells were attenuated by IGF1, which further confirmed IGF1R was the downstream target of BUP in SH-SY5Y cells.

Conclusion: In the present study, miR-132 played important roles in regulating BUP-induced neurotoxicity through IGF1R and may act as a promising molecular target for the treatment of human neurotoxicity induced by BUP.

Keywords: Apoptosis; Bupivacaine; Neurotoxicity; miRNA.

MeSH terms

  • Anesthetics, Local / toxicity*
  • Apoptosis / drug effects
  • Bupivacaine / toxicity*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Flow Cytometry
  • Humans
  • MicroRNAs / genetics*
  • Neuroblastoma / metabolism
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / genetics
  • Receptor, IGF Type 1
  • Receptors, Somatomedin / metabolism
  • Up-Regulation / genetics


  • Anesthetics, Local
  • IGF1R protein, human
  • MIRN132 microRNA, human
  • MicroRNAs
  • Receptors, Somatomedin
  • Receptor, IGF Type 1
  • Bupivacaine