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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

[ Vol. 16 , Issue. 7 ]

Author(s):

Peizhi Ma, Yuanlong Li*, Wei Zhang, Fengqin Fang, Jun Sun, Mingzhou Liu, Kun Li and Lingfang Dong   Pages 596 - 612 ( 17 )

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:

Lnc-MALAT1, Alzheimer's disease, Neuron apoptosis, Neuroinflammation, neurite outgrowth, miR-125b.

Affiliation:

Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou



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