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 - PubMed (original) (raw)
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
Peizhi Ma et al. Curr Alzheimer Res. 2019.
Abstract
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.
Keywords: Alzheimer's disease; Lnc-MALAT1; Neuroinflammation; Neuron apoptosis; miR-125b; neurite outgrowth..
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