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Current Alzheimer Research

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

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

Author(s): Peizhi Ma, Yuanlong Li*, Wei Zhang, Fengqin Fang, Jun Sun, Mingzhou Liu, Kun Li and Lingfang Dong

Volume 16, Issue 7, 2019

Page: [596 - 612] Pages: 17

DOI: 10.2174/1567205016666190725130134

open access plus

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.

« Previous Next »
[1]
Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur J Neurol 25(1): 59-70. (2018)
[http://dx.doi.org/10.1111/ene.13439] [PMID: 28872215]
[2]
Scheltens P, Blennow K, Breteler MM. de Strooper B4, Frisoni GB5, Salloway S, et al Alzheimer’s disease. Lancet 388(10043): 505-17. (2016)
[http://dx.doi.org/10.1016/S0140-6736(15)01124-1] [PMID: 26921134]
[3]
Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 9(1): 63-75.e2. (2013)
[http://dx.doi.org/10.1016/j.jalz.2012.11.007]
[4]
Alzheimer’s Association Report. 2017 Alzheimer’s disease facts and figures. Alzheimers Dement 13(4): 325-73. (2017)
[http://dx.doi.org/10.1016/j.jalz.2017.02.001]
[5]
Feng SD, Yang JH, Yao CH, Yang SS, Zhu ZM, Wu D, et al. Potential regulatory mechanisms of lncRNA in diabetes and its complications. Biochem Cell Biol 95(3): 361-7. (2017)
[http://dx.doi.org/10.1139/bcb-2016-0110] [PMID: 28177764]
[6]
Woo CJ, Maier VK, Davey R, Brennan J, Li G, Brothers J, et al. Gene activation of SMN by selective disruption of lncRNA-mediated recruitment of PRC2 for the treatment of spinal muscular atrophy. Proc Natl Acad Sci USA 114(8): E1509-18. (2017)
[http://dx.doi.org/10.1073/pnas.1616521114] [PMID: 28193854]
[7]
Wei GH, Wang X. lncRNA MEG3 inhibit proliferation and metastasis of gastric cancer via p53 signaling pathway. Eur Rev Med Pharmacol Sci 21(17): 3850-6. (2017)
[PMID: 28975980]
[8]
Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, et al. Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat Med 14(7): 723-30. (2008)
[http://dx.doi.org/10.1038/nm1784] [PMID: 18587408]
[9]
Ciarlo E, Massone S, Penna I, Nizzari M, Gigoni A, Dieci G, et al. An intronic ncRNA-dependent regulation of SORL1 expression affecting Aβ formation is upregulated in post-mortem Alzheimer’s disease brain samples. Dis Model Mech 6(2): 424-33. (2013)
[http://dx.doi.org/10.1242/dmm.009761] [PMID: 22996644]
[10]
Ji P, Diederichs S, Wang W, Böing S, Metzger R, Schneider PM, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 22(39): 8031-41. (2003)
[http://dx.doi.org/10.1038/sj.onc.1206928] [PMID: 12970751]
[11]
Jin Y, Feng SJ, Qiu S, Shao N, Zheng JH. LncRNA MALAT1 promotes proliferation and metastasis in epithelial ovarian cancer via the PI3K-AKT pathway. Eur Rev Med Pharmacol Sci 21(14): 3176-84. (2017)
[PMID: 28770968]
[12]
Li L, Chen H, Gao Y, et al. Long noncoding RNA MALAT1 promotes aggressive pancreatic cancer proliferation and metastasis via the stimulation of autophagy. Mol Cancer Ther 15(9): 2232-43. (2016)
[http://dx.doi.org/10.1158/1535-7163.MCT-16-0008] [PMID: 27371730]
[13]
Qiao Y, Peng C, Li J, Wu D, Wang X. LncRNA MALAT1 is neuroprotective in a rat model of spinal cord ischemia-reperfusion injury through miR-204 regulation. Curr Neurovasc Res 15(3): 211-9. (2018)
[http://dx.doi.org/10.2174/1567202615666180712153150] [PMID: 29998804]
[14]
Masoumi F, Ghorbani S, Talebi F, Branton WG. Rajaei, Power C, et al Malat1 long noncoding RNA regulates inflammation and leukocyte differentiation in experimental autoimmune encephalomyelitis. J Neuroimmunol 328: 50-9. (2019)
[http://dx.doi.org/10.1016/j.jneuroim.2018.11.013] [PMID: 30583215]
[15]
Yang H, Wang H, Shu Y, Li X. miR-103 Promotes neurite outgrowth and suppresses cells apoptosis by targeting prostaglandin-endoperoxide synthase 2 in cellular models of Alzheimer’s disease. Front Cell Neurosci 12: 91. (2018)
[http://dx.doi.org/10.3389/fncel.2018.00091] [PMID: 29674956]
[16]
Chen H, Wang X, Yan X, Cheng X, He X, Zheng W. LncRNA MALAT1 regulates sepsis-induced cardiac inflammation and dysfunction via interaction with miR-125b and p38 MAPK/NFκB. Int Immunopharmacol 55: 69-76. (2018)
[http://dx.doi.org/10.1016/j.intimp.2017.11.038] [PMID: 29227823]
[17]
Xie H, Liao X, Chen Z, Fang Y, He A, Zhong Y, et al. LncRNA MALAT1 Inhibits apoptosis and promotes invasion by antagonizing miR-125b in bladder cancer cells. J Cancer 8(18): 3803-11. (2017)
[http://dx.doi.org/10.7150/jca.21228] [PMID: 29151968]
[18]
Chang SM, Hu WW. Long non-coding RNA MALAT1 promotes oral squamous cell carcinoma development via microRNA-125b/STAT3 axis. J Cell Physiol 233(4): 3384-96. (2018)
[http://dx.doi.org/10.1002/jcp.26185] [PMID: 28926115]
[19]
Jin Y, Tu Q, Liu M. MicroRNA125b regulates Alzheimer’s disease through SphK1 regulation. Mol Med Rep 18(2): 2373-80. (2018)
[http://dx.doi.org/10.3892/mmr.2018.9156] [PMID: 29901156]
[20]
Ma X, Liu L, Meng J. MicroRNA-125b promotes neurons cell apoptosis and Tau phosphorylation in Alzheimer’s disease. Neurosci Lett 661: 57-62. (2017)
[http://dx.doi.org/10.1016/j.neulet.2017.09.043] [PMID: 28947385]
[21]
Hong H, Li Y, Su B. Identification of circulating miR-125b as a potential biomarker of Alzheimer’s disease in APP/PS1 transgenic mouse. J Alzheimers Dis 59(4): 1449-58. (2017)
[http://dx.doi.org/10.3233/JAD-170156] [PMID: 28731435]
[22]
Banzhaf-Strathmann J, Benito E, May S, Arzberger T, Tahirovic S, Kretzschmar H, et al. MicroRNA-125b induces tau hyperphos-phorylation and cognitive deficits in Alzheimer’s disease. EMBO J 33(15): 1667-80. (2014)
[http://dx.doi.org/10.15252/embj.201387576] [PMID: 25001178]
[23]
Mathis CA, Wang Y, Klunk WE. Imaging beta-amyloid plaques and neurofibrillary tangles in the aging human brain. Curr Pharm Des 10(13): 1469-92. (2004)
[http://dx.doi.org/10.2174/1381612043384772] [PMID: 15134570]
[24]
Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol 14(4): 388-405. (2015)
[http://dx.doi.org/10.1016/S1474-4422(15)70016-5] [PMID: 25792098]
[25]
Butterfield DA, Reed T, Newman SF, Sultana R. Roles of amyloid beta-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer’s disease and mild cognitive impairment. Free Radic Biol Med 43(5): 658-77. (2007)
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.05.037] [PMID: 17664130]
[26]
Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580): 353-6. (2002)
[http://dx.doi.org/10.1126/science.1072994] [PMID: 12130773]
[27]
Wu J, Chen L, Zheng C, Xu S, Gao Y, Wang J. Co-expression network analysis revealing the potential regulatory roles of lncRNAs in Alzheimer’s disease. Interdiscip Sci (2019)
[http://dx.doi.org/10.1007/s12539-019-00319-w] [PMID: 30715720]
[28]
Eißmann M, Gutschner T, Hämmerle M, Günther S, Caudron-Herger M, Groß M, et al. Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development. RNA Biol 9(8): 1076-87. (2012)
[http://dx.doi.org/10.4161/rna.21089] [PMID: 22858678]
[29]
Jiang LT, Wan CH, Guo QH, Yang SJ, Wu JD, Cai J. Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) Promotes Renal Cell Carcinoma Progression via Sponging miRNA-429. Med Sci Monit 24: 1794-801. (2018)
[http://dx.doi.org/10.12659/MSM.909450] [PMID: 29588438]
[30]
Li S, Sun Y, Zhong L, Xiao Z, Yang M, Chen M, et al. The suppression of ox-LDL-induced inflammatory cytokine release and apoptosis of HCAECs by long non-coding RNA-MALAT1 via regulating microRNA-155/SOCS1 pathway. Nutr Metab Cardiovasc Dis 28(11): 1175-87. (2018)
[http://dx.doi.org/10.1016/j.numecd.2018.06.017] [PMID: 30314869]
[31]
Abe M, Bonini NM. MicroRNAs and neurodegeneration: role and impact. Trends Cell Biol 23(1): 30-6. (2013)
[http://dx.doi.org/10.1016/j.tcb.2012.08.013] [PMID: 23026030]
[32]
Liu F, Shi J, Tanimukai H, Gu J, Gu J, Grundke-Iqbal I, et al. Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer’s disease. Brain 132(Pt 7): 1820-32. (2009)
[http://dx.doi.org/10.1093/brain/awp099] [PMID: 19451179]

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