lncRNA KCNQ1OT1靶向调控miR-132-5p对帕金森病细胞损伤的保护机制

Protective mechanism of lncRNA KCNQ1OT1 targeting miR-132-5p against cell damage in Parkinson’s disease

目的探究长链非编码RNA KCNQ1OT1(lncRNA KCNQ1OT1)靶向调控微小RNA-132-5p(miR-132-5p)对帕金森病细胞损伤的保护机制。方法SH-SY5Y细胞通过1-甲基-4-苯基吡啶阳离子(MMP+)诱导建立帕金森病细胞模型,检测SH-SY5Y细胞中lncRNA KCNQ1OT1、miR-132-5p表达、活性氧(ROS)、超氧化物歧化酶(SOD)、丙二醛(MDA)、白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平、凋亡率及Bcl-2、Bax蛋白表达,验证lncRNA KCNQ1OT1、miR-132-5p的调控关系。结果与Con组相比,MMP+组lncRNA KCNQ1OT1、miR-132-5p表达量较高(P<0.05)。低表达lncRNA KCNQ1OT1、干扰miR-132-5p表达均可减轻MMP+诱导的SH-SY5Y细胞氧化应激及炎性损伤,抑制细胞死亡,lncRNA KCNQ1OT1靶向正调控miR-132-5p表达,miR-132-5p过表达逆转了lncRNA KCNQ1OT1低表达对MMP+诱导SK-N-SH细胞氧化应激、炎症损伤及凋亡。结论lncRNA KCNQ1OT1通过靶向抑制miR-132-5p表达减轻了MMP+诱导SK-N-SH细胞氧化应激、炎症损伤,抑制了细胞凋亡。

Objective To explore the protective mechanism of long non-coding RNA KCNQ1OT1(lncRNA KCNQ1OT1)targeting microRNA-132-5p(miR-132-5p)against cell damage in Parkinson’s disease.Methods SH-SY5Y cells were induced with 1-methyl-4-phenylpyridinium ion(MPP+)to establish a cell model of Parkinson’s disease or blank control.The expression of lncRNA KCNQ1OT1,miR-132-5p,reactive oxygen species(ROS),superoxide dismutase(SOD),malondialdehyde(MDA),interleukin-1β(IL-1β),interleukin-6(IL-6)tumor necrosis factor-α(TNF-α),apoptosis rate,and the expression of B-cell lymphoma2(BCL-2)and Bax proteins in SH-SY5Y cells were detected,aiming to verify the regulatory relationship between lncRNA KCNQ1OT1 and miR-132-5p.Results Compared with control(Con)group,the expression levels of lncRNA KCNQ1OT1 and miR-132-5p in MMP+group were significantly higher(P<0.05).Both low expression of lncRNA KCNQ1OT1 and interference with expression of miR-132-5p could alleviate MMP+-induced oxidative stress and inflammatory damage of SH-SY5Y cells,inhibit cell death,and positively regulate expression of miR-132-5p by targeting lncRNA KCNQ1OT1.Over-expression of miR-132-5p reversed the oxidative stress,inflammatory damage and apoptosis of MMP+-induced SK-N-SH cells by low expression of lncRNA KCNQ1OT1.Conclusion LncRNA KCNQ1OT1 alleviated the oxidative stress,inflammatory damage,and apoptosis of MMP+-induced SK-N-SH cells by targeted inhibition of miR-132-5p expression.