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NEAT1 Decreasing Suppresses Parkinson's Disease Progression via Acting as miR-1301-3p Sponge.
- Source :
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Journal of molecular neuroscience : MN [J Mol Neurosci] 2021 Feb; Vol. 71 (2), pp. 369-378. Date of Electronic Publication: 2020 Jul 25. - Publication Year :
- 2021
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Abstract
- Long non-coding RNA (lncRNA) plays a crucial role in multiple disorders, while the role of it in Parkinson's disease (PD) is still unclear. Here, the increased lncRNA NEAT1 was discovered in MPP <superscript>+</superscript> -induced SH-SY5Y cells. Then, we proved that NEAT1 decreasing suppressed MPP <superscript>+</superscript> -induced neuronal apoptosis, upregulation of α-syn and activation of NLRP3 inflammasome. Rescue experiments shown that the inhibition of NEAT1 decreasing to MPP <superscript>+</superscript> -induced activation of NLRP3 inflammasome and subsequent neuronal apoptosis can be reversed by overexpressed α-syn. Subsequently, we indicated the interaction between NEAT1 and miR-1301-3p, as well as between NEAT1 and miR-5047. Interesting, we found that NEAT1 decreasing repressed the expression of GJB1, a downstream target of miR-1301-3p and miR-5047, through promoting miR-1301-3p rather than miR-5047 expression. Finally, we transfected miR-1301-3p inhibitor to MPP <superscript>+</superscript> -induced SH-SY5Y cells following si-NEAT1, and found that downregulation of NEAT1 repressed α-syn-mediated the activation of NLRP3 inflammasome through regulating miR-1301-3p/GJB1 signaling pathway. Overall, our data demonstrated that NEAT1 decreasing effectively suppressed MPP <superscript>+</superscript> -induced neuronal apoptosis. Mechanismly, downregulation of NEAT1 repressed α-syn-induced activation of NLRP3 inflammasome via inhibiting the expression of GJB1 by targeting miR-1301-3p. Our study supported a new and reliable evidence for lncRNA NEAT1 as a potential target for PD treatment.
- Subjects :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine pharmacology
Apoptosis drug effects
Apoptosis Regulatory Proteins biosynthesis
Apoptosis Regulatory Proteins genetics
Cell Line
Connexins biosynthesis
Connexins genetics
Disease Progression
Down-Regulation
Gene Expression Regulation drug effects
Gene Knockdown Techniques
Humans
Inflammasomes physiology
MicroRNAs genetics
NLR Family, Pyrin Domain-Containing 3 Protein antagonists & inhibitors
NLR Family, Pyrin Domain-Containing 3 Protein biosynthesis
NLR Family, Pyrin Domain-Containing 3 Protein genetics
Neurons drug effects
Neurons metabolism
RNA, Long Noncoding biosynthesis
Signal Transduction
alpha-Synuclein physiology
Gap Junction beta-1 Protein
MicroRNAs antagonists & inhibitors
Parkinson Disease genetics
RNA, Long Noncoding genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1166
- Volume :
- 71
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of molecular neuroscience : MN
- Publication Type :
- Academic Journal
- Accession number :
- 32712773
- Full Text :
- https://doi.org/10.1007/s12031-020-01660-2