NEAT1 Decreasing Suppresses Parkinson’s Disease Progression via Acting as miR-1301-3p Sponge

• Published in: Journal of molecular neuroscience Vol. 71; no. 2; pp. 369 - 378
• Main Authors: Sun, Qiang, Zhang, Yueliang, Wang, Songlin, Yang, Fang, Cai, Hongxia, Xing, Yu, Chen, Zengfeng, Chen, Jun
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2021; Springer Nature B.V
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology; alpha-Synuclein - physiology; Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - biosynthesis; Apoptosis Regulatory Proteins - genetics; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Line; Connexins - biosynthesis; Connexins - genetics; Disease Progression; Down-Regulation; Gap Junction beta-1 Protein; Gene Expression Regulation - drug effects; Gene Knockdown Techniques; Humans; Inflammasomes; Inflammasomes - physiology; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; Movement disorders; MPP; Neurochemistry; Neurodegenerative diseases; Neurology; Neurons - drug effects; Neurons - metabolism; Neurosciences; 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; Non-coding RNA; Parkinson Disease - genetics; Parkinson's disease; Proteomics; RNA, Long Noncoding - biosynthesis; RNA, Long Noncoding - genetics; Signal Transduction; Parkinson disease; Nuclear enriched assembly transcript 1; Neuronal apoptosis; NLRP3 inflammasome; Endogenous competing RNA
• ISSN: 0895-8696; 1559-1166; 1559-1166
• DOI: 10.1007/s12031-020-01660-2

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 + -induced SH-SY5Y cells. Then, we proved that NEAT1 decreasing suppressed MPP + -induced neuronal apoptosis, upregulation of α-syn and activation of NLRP3 inflammasome. Rescue experiments shown that the inhibition of NEAT1 decreasing to MPP + -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 + -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 + -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.