Long Non-coding RNA MALAT1 Inhibits Neuron Apoptosis and Neuroinflammation While Stimulates Neurite Outgrowth and Its Correlation With MiR-125b Mediates PTGS2, CDK5 and FOXQ1 in Alzheimer's Disease
Long Non-coding RNA MALAT1 Inhibits Neuron Apoptosis and Neuroinflammation While Stimulates Neurite Outgrowth and Its Correlation With MiR-125b Mediates PTGS2, CDK5 and FOXQ1 in Alzheimer's Disease
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DOI：
10.2174/1567205016666190725130134
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发表时间：
2019-01-01
影响因子：
2.1
通讯作者：
Dong, Lingfang
中科院分区：
文献类型：
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作者：
Ma, Peizhi;Li, Yuanlong;Dong, Lingfang
背景：本研究旨在研究长非编码核糖核酸转移相关肺腺癌转录本1(Lnc-MALAT1)在阿尔茨海默病(AD)中对神经元凋亡、突起生长和炎症的调控作用，并进一步探讨其分子机制。方法：将对照、LNC-MALAT1、对照shRNA和LNC-MALAT1 shRNA分别转入NOF刺激的PC12细胞AD模型和Aβ1-42诱导的原代大鼠胚胎大脑皮层神经元AD模型。通过转移lnc-MALAT1过表达、lnc-MALAT1过表达和miR-125b过表达质粒进行补救实验。用Hoechst-PI/凋亡标记物检测神经元的凋亡、突起生长和炎症反应，并用显微镜和RT-qPCR/Western印迹方法进行观察。结果：在两种AD模型中，lnc-MALAT1过表达抑制神经细胞凋亡，促进轴突生长，降低IL-6和TNF-α水平，升高IL-10水平，与对照shRNA相比，lnc-MALAT1基因敲除促进神经元凋亡，抑制突起生长，升高IL-6和TNF-α水平，但降低IL-10水平。此外，lnc-MALAT1反向调节miR-125b的表达，而miR-125b不影响lnc-Malati的表达。随后的抢救实验显示，miR-125b可诱导AD模型神经元凋亡，抑制轴突生长，促进炎症反应，增加Ptgs2和CDK5的表达，降低FOXQ1的表达。结论：LNC-MALAT1可能与miR-125b相互作用，抑制AD模型神经元的凋亡和炎症，促进轴突生长。
Background: This study aimed to investigate the effect of long noncoding ribonucleic acids (RNAs) metastasis-associated lung adenocarcinoma transcript 1 (lnc-MALAT1) on regulating neuron apoptosis, neurite outgrowth and inflammation, and further explore its molecule mechanism in Alzheimer's disease (AD).Methods: Control overexpression, lnc-MALAT1 overexpression, control shRNA, and lnc-MALAT1 shRNA were transfected into NOF-stimulated PC12 cellular AD model and cellular AD model from primary cerebral cortex neurons of rat embryo, which were established by A beta 1-42 insult. Rescue experiments were performed by transferring lnc-MALAT1 overexpression and lnc-MALAT1 overexpression & miR-125b overexpression plasmids. Neuron apoptosis, neurite outgrowth and inflammation were detected by Hoechst-PI/apoptosis marker expressions, and observations were made using microscope and RT-qPCR/Western blot assays. PTGS2, CDK5 and FOXQ1 expressions in rescue experiments were also determined.Results: In two AD models, lnc-MALAT1 overexpression inhibited neuron apoptosis, promoted neurite outgrowth, reduced IL-6 and TNF-alpha levels, and increased IL-10 level compared to control overexpression, while lnc-MALAT1 knockdown promoted neuron apoptosis, repressed neurite outgrowth, elevated IL-6 and TNF-alpha levels, but reduced IL-10 level compared to control shRNA. Additionally, lnc-MALAT1 reversely regulated miR-125b expression, while miR-125b did not influence the lnc-MALATI expression. Subsequently, rescue experiments revealed that miR-125b induced neuron apoptosis, inhibited neurite outgrowth and promoted inflammation, also increased PTGS2 and CDK5 expressions but decreased FOXQ1 expression in lnc-MALAT1 overexpression treated AD models.Conclusion: Lnc-MALAT1 might interact with miR-125b to inhibit neuron apoptosis and inflammation while promote neurite outgrowth in AD.