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+-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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adriaens C, Rambow F (2019) The long noncoding RNA NEAT1_1 is seemingly dispensable for normal tissue homeostasis and cancer cell growth. RNA 25(12):1681–1695
Balestrino R, Schapira AHV (2018) Glucocerebrosidase and Parkinson disease: molecular, clinical, and therapeutic implications. Neuroscientist 24(5):540–559
Boros FA, Maszlag-Török R, Vécsei L, Klivényi P (2020) Increased level of NEAT1 long non-coding RNA is detectable in peripheral blood cells of patients with Parkinson's disease. Brain Res 1730:146672
Ding XM, Zhao LJ, Qiao HY, Wu SL, Wang XH (2019) Long non-coding RNA-p21 regulates MPP(+)-induced neuronal injury by targeting miR-625 and derepressing TRPM2 in SH-SY5Y cells. Chem Biol Interact 307:73–81
Gordon R, Albornoz EA (2018) Inflammasome inhibition prevents alpha-synuclein pathology and dopaminergic neurodegeneration in mice. Sci Transl Med 10(465):eaah4066
Gustot A, Gallea JI, Sarroukh R, Celej MS, Ruysschaert JM, Raussens V (2015) Amyloid fibrils are the molecular trigger of inflammation in Parkinson's disease. Biochem J 471(3):323–333
Haque ME, Akther M, Jakaria M, Kim IS, Azam S, Choi DK (2020) Targeting the microglial NLRP3 inflammasome and its role in Parkinson's disease. Mov Disord 35(1):20–33
Jankovic J, Goodman I, Safirstein B, Marmon TK, Schenk DB, Koller M, Zago W, Ness DK, Griffith SG, Grundman M, Soto J, Ostrowitzki S, Boess FG, Martin-Facklam M, Quinn JF, Isaacson SH, Omidvar O, Ellenbogen A, Kinney GG (2018) Safety and tolerability of multiple ascending doses of PRX002/RG7935, an anti-alpha-synuclein monoclonal antibody, in patients with Parkinson disease: a randomized clinical trial. JAMA Neurol 75(10):1206–1214
Jiang S, Cheng SJ, Ren LC, Wang Q, Kang YJ, Ding Y, Hou M, Yang XX, Lin Y, Liang N, Gao G (2019) An expanded landscape of human long noncoding RNA. Nucleic Acids Res 47(15):7842–7856
Klec C, Prinz F, Pichler M (2019) Involvement of the long noncoding RNA NEAT1 in carcinogenesis. Mol Oncol 13(1):46–60
Nussbaum RL (2017) The identification of alpha-Synuclein as the first Parkinson disease gene. J Park Dis 7(s1):S43–s49
Peng T, Liu X, Wang J, Liu Y, Fu Z, Ma X, Li J, Sun G, Ji Y, Lu J, Wan W, Lu H (2019) Long noncoding RNA HAGLROS regulates apoptosis and autophagy in Parkinson's disease via regulating miR-100/ATG10 axis and PI3K/Akt/mTOR pathway activation. Artif Cells Nanomed Biotechnol 47(1):2764–2774
Qian C, Ye Y, Mao H, Yao L, Sun X, Wang B, Zhang H, Xie L, Zhang H, Zhang Y, Zhang S, He X (2019) Downregulated lncRNA-SNHG1 enhances autophagy and prevents cell death through the miR-221/222 /p27/mTOR pathway in Parkinson's disease. Exp Cell Res 384(1):111614
Reyes JF, Sackmann C, Hoffmann A, Svenningsson P, Winkler J, Ingelsson M, Hallbeck M (2019) Binding of alpha-synuclein oligomers to Cx32 facilitates protein uptake and transfer in neurons and oligodendrocytes. Acta Neuropathol 138(1):23–47
Schenkman M, Moore CG, Kohrt WM, Hall DA, Delitto A, Comella CL, Josbeno DA, Christiansen CL, Berman BD, Kluger BM, Melanson EL, Jain S, Robichaud JA, Poon C, Corcos DM (2018) Effect of high-intensity treadmill exercise on motor symptoms in patients with de novo Parkinson disease: a phase 2 randomized clinical trial. JAMA Neurol 75(2):219–226
Seppi K, Ray Chaudhuri K (2019) Update on treatments for nonmotor symptoms of Parkinson's disease-an evidence-based medicine review. Mov Disord 34(2):180–198
Simchovitz A, Hanan M, Niederhoffer N, Madrer N, Yayon N, Bennett ER, Greenberg DS, Kadener S, Soreq H (2019) NEAT1 is overexpressed in Parkinson's disease substantia nigra and confers drug-inducible neuroprotection from oxidative stress. FASEB J 33(10):11223–11234
Simchovitz A, Hanan M, Yayon N, Lee S, Bennett ER, Greenberg DS, Kadener S, Soreq H (2020) A lncRNA survey finds increases in neuroprotective LINC-PINT in Parkinson's disease substantia nigra. Aging Cell 19(3):e13115
Wang Z, Zhao Y, Xu N, Zhang S, Wang S, Mao Y, Zhu Y, Li B, Jiang Y, Tan Y, Xie W, Yang BB, Zhang Y (2019) NEAT1 regulates neuroglial cell mediating Abeta clearance via the epigenetic regulation of endocytosis-related genes expression. Cell Mol Life Sci 76(15):3005–3018
Wang Z, Li K, Huang W (2020) Long non-coding RNA NEAT1-centric gene regulation. Cell Mol Life Sci. https://doi.org/10.1007/s00018-020-03503-0
Wu S, Yao W, Chen C, Chen H, Huang F, Liu Y, Cai J, Yuan D, Hei Z (2020) Connexin 32 deficiency protects the liver against ischemia/reperfusion injury. Eur J Pharmacol 876:173056
Xie SP, Zhou F, Li J, Duan SJ (2019) NEAT1 regulates MPP(+)-induced neuronal injury by targeting miR-124 in neuroblastoma cells. Neurosci Lett 708:134340
Xiong WX, Sun YM, Guan RY, Luo SS, Chen C, An Y, Wang J, Wu JJ (2016) The heterozygous A53T mutation in the alpha-synuclein gene in a Chinese Han patient with Parkinson disease: case report and literature review. J Neurol 263(10):1984–1992
Xu X, Zhuang C, Wu Z, Qiu H, Feng H, Wu J (2018) LincRNA-p21 inhibits cell viability and promotes cell apoptosis in Parkinson's disease through activating α-Synuclein expression. Biomed Res Int 2018:8181374
Yan W, Chen ZY, Chen JQ, Chen HM (2018) LncRNA NEAT1 promotes autophagy in MPTP-induced Parkinson's disease through stabilizing PINK1 protein. Biochem Biophys Res Commun 496(4):1019–1024
Yu X, Li Z (2017) NEAT1: a novel cancer-related long non-coding RNA. Cell Prolif 50(2)
Zhang Z, Yao W, Yuan D, Huang F, Liu Y, Luo G, Hei Z (2020) Effects of Connexin 32-mediated lung inflammation resolution during liver ischemia reperfusion. Dig Dis Sci. https://doi.org/10.1007/s10620-019-06020-8
Zhou Y, Lu M, Du RH, Qiao C, Jiang CY, Zhang KZ, Ding JH, Hu G (2016) MicroRNA-7 targets nod-like receptor protein 3 inflammasome to modulate neuroinflammation in the pathogenesis of Parkinson's disease. Mol Neurodegener 11:28
Funding
None.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing Interests
The authors declare that they have no competing interests.
Consent for Publication
All of the authors have given their consent for publication.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Sun, Q., Zhang, Y., Wang, S. et al. NEAT1 Decreasing Suppresses Parkinson’s Disease Progression via Acting as miR-1301-3p Sponge. J Mol Neurosci 71, 369–378 (2021). https://doi.org/10.1007/s12031-020-01660-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-020-01660-2