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

被引:25
作者
Sun, Qiang [1 ]
Zhang, Yueliang [1 ]
Wang, Songlin [1 ]
Yang, Fang [2 ]
Cai, Hongxia [3 ]
Xing, Yu [4 ]
Chen, Zengfeng [5 ]
Chen, Jun [1 ]
机构
[1] Hubei Univ Med, TaiHe Hosp, Dept Neurol, 32 Renmin South Rd, Shiyan 442000, Hubei, Peoples R China
[2] Hubei Univ Med, TaiHe Hosp, Dept Oncol, 32 Renmin South Rd, Shiyan 442000, Hubei, Peoples R China
[3] Hubei Univ Med, TaiHe Hosp, Dept Obstet & Gynecol, 32 Renmin South Rd, Shiyan 442000, Hubei, Peoples R China
[4] Hubei Univ Med, TaiHe Hosp, Dept Med Image Ctr, 32 Renmin South Rd, Shiyan 442000, Hubei, Peoples R China
[5] Hubei Univ Med, TaiHe Hosp, Chron Dis Rehabil Ctr 1, 32 Renmin South Rd, Shiyan 442000, Hubei, Peoples R China
关键词
Parkinson disease; Nuclear enriched assembly transcript 1; Endogenous competing RNA; NLRP3; inflammasome; Neuronal apoptosis; ALPHA-SYNUCLEIN; AUTOPHAGY;
D O I
10.1007/s12031-020-01660-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 alpha-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 alpha-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 alpha-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 alpha-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.
引用
收藏
页码:369 / 378
页数:10
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