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 NGF-stimulated PC12 cellular AD model and cellular AD model from primary cerebral cortex neurons of rat embryo, which were established by Aβ1-42 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-α 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-α 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- MALAT1 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.

中文翻译：

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长的非编码RNA MALAT1抑制神经元凋亡和神经炎症，同时刺激神经突生长及其与MiR-125b的相关性介导了阿尔茨海默氏病的PTGS2，CDK5和FOXQ1。

背景：本研究旨在探讨长期非编码核糖核酸（RNA）转移相关的肺腺癌转录本1（lnc-MALAT1）对调节神经元凋亡，神经突向外生长和炎症的影响，并进一步探讨其在阿尔茨海默氏病（AD）中的分子机制。 。方法将对照过表达，lnc-MALAT1过表达，对照shRNA和lnc-MALAT1 shRNA分别转入NGF刺激的大鼠胚原代大脑皮层神经元PC12细胞AD模型和细胞AD模型，并通过Aβ1-42损伤建立。通过转移lnc-MALAT1过表达和lnc-MALAT1过表达和miR-125b过表达质粒进行抢救实验。通过Hoechst-PI /凋亡标记物表达检测神经元凋亡，神经突生长和炎症，并使用显微镜和RT-qPCR / Western印迹法进行观察。还确定了救援实验中的PTGS2，CDK5和FOXQ1表达。结果在两个AD模型中，与对照过表达相比，lnc-MALAT1的过表达抑制神经元凋亡，促进神经突生长，降低IL-6和TNF-α水平，并增加IL-10水平，而lnc-MALAT1敲低则促进神经元凋亡，抑制神经突。与对照shRNA相比，IL-6和TNF-α水平升高，但IL-10水平降低。另外，lnc-MALAT1反向调节miR-125b的表达，而miR-125b则不影响lnc-MALAT1的表达。随后，救援实验表明，miR-125b诱导神经元凋亡，抑制神经突生长并促进炎症，在lnc-MALAT1过表达治疗的AD模型中，PTGS2和CDK5表达也增加，但FOXQ1表达降低。结论Lnc-MALAT1可能与miR-125b相互作用，抑制神经元凋亡和炎症，同时促进AD中神经突的生长。