Knockdown of lincRNA PADNA promotes bupivacaine-induced neurotoxicity by miR-194/FBXW7 axis

Fan Yuning,Nan Zhenhua,Wang Tenghuan,Gong Shengkai,Chen Liang

doi:10.1186/s10020-020-00209-8

Abstract

BackgroundThe aim of the study was to explore the function and mechanism of lincRNA PADNA in bupivacaine-induced neurotoxicity.MethodsMouse DRG neurons were cultured in vitro and treated with bupivacaine to establish a neurotoxicity model. Caspase3 activity, cell viability, and TUNEL assays were analyzed to assess the role of lincRNA PADNA. A dual-luciferase reporter assay was used to determine the binding target of lincRNA PANDA.ResultsThe expression of lincRNA PADNA was significantly increased with increasing concentrations of bupivacaine. Functional analysis revealed that knockdown of lincRNA PADNA increased caspase3 activity and inhibited cell viability. Western blot analysis showed that knockdown of lincRNA PADNA promoted cleaved caspase3 levels. We also revealed that lincRNA PADNA may bind with miR-194. Knockdown of miR-194 rescued the function of lincRNA PADNA, suggesting that lincRNA PADNA may sponge miR-194. In addition, we provided new evidence that the lincRNA PADNA/miR-194/FBXW7 axis plays an important role in the neurotoxicity process.ConclusionWe performed comprehensive experiments to verify the function and mechanism of lincRNA PADNA in bupivacaine-induced neurotoxicity. Our study provides new evidence and clues for the prevention of neurotoxicity.

Highlights

Bupivacaine is one of the most commonly used anesthetics for local infiltration anesthesia (Radwan et al 2002; Guo et al 2017; Chalkiadis et al 2016)
To investigate the underlying mechanism of how lincRNA Protect cell death RNA (PADNA) participates in bupivacaine-induced neurotoxicity, we conducted bioinformatics analysis, and the results revealed that lincRNA PADNA played a protective role through inhibition of the progression of bupivacaine-induced neurotoxicity by sponging miR194, which has been reported to inhibit tumor progression (Wu et al 2014). miR-194 was predicted to target the 3’untranslated region (UTR) of the cancer-related protein F-box and WD repeat domain containing 7 (FBXW7) by analysis in StarBase2.0
Our experiments demonstrated that lincRNA PADNA played a protective role in bupivacaine-induced neurotoxicity

Summary

Introduction

Bupivacaine is one of the most commonly used anesthetics for local infiltration anesthesia (Radwan et al 2002; Guo et al 2017; Chalkiadis et al 2016). During the past few decades, bupivacaine has been found to be neurotoxic in the setting of local injection, causing symptoms such as paralysis, paresthesia, hypoventilation, Efforts have been made to investigate the association between bupivacaine-induced neurotoxicity and noncoding RNAs (ncRNAs) (Wang et al 2015). LncRNAs are defined as transcripts with lengths exceeding 200 nucleotides (Song et al 2017), which have been widely studied and found to be abundantly and functionally important in regulating the cell cycle (Liu et al 2015), cell metabolism (Zhang et al 2016a) and related diseases such as malignant tumors (Gu et al 2018). The role of lncRNAs in bupivacaine-induced neurotoxicity has rarely been researched. The aim of the study was to explore the function and mechanism of lincRNA PADNA in bupivacaineinduced neurotoxicity

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