circ_0000018 downregulation peripherally ameliorates neuroprotection against acute ischemic stroke through the miR‑871/BCL2L11 axis

Jiang,Min; Wang,Xiao-Bin; Jiang,Shan

doi:10.3892/mmr.2023.13107

circ_0000018 downregulation peripherally ameliorates neuroprotection against acute ischemic stroke through the miR‑871/BCL2L11 axis

Authors:
- Min Jiang
- Xiao-Bin Wang
- Shan Jiang
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Affiliations: Laboratory Animal Centre, Southeastern University, Nanjing, Jiangsu 210003, P.R. China
Published online on: September 28, 2023 https://doi.org/10.3892/mmr.2023.13107
Article Number: 220
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute ischemic stroke (AIS) is a common acute cerebrovascular disease. Circular RNAs (circRNAs) have been demonstrated to have critical functions in a wide range of physiological processes and disorders in humans. However, their precise function in ischemic stroke (IS) remains largely unknown. The present study explored the function and potential mechanisms of circ_0000018 in AIS in vivo and in vitro. The cerebral ischemia/reperfusion injury model was established in vivo and in vitro using the oxygen‑glucose deprivation (OGD/R) and transient middle cerebral artery occlusion (tMCAO) methods. Subsequently, the impact of circ_0000018 on cerebral ischemia/reperfusion injury was assessed using various techniques, including TTC staining, quantitative PCR, western blotting, cell counting kit‑8 assay, Annexin V‑FITC Apoptosis Detection Kit, luciferase reporter gene assays, and others. The levels of circ_0000018 were markedly increased in the OGD/R‑treated neuronal cells and in a mouse model of tMCAO. The blocking of microRNA (miR)‑871 by circ_0000018 promoted Bcl‑2‑like protein 11 (BCL2L11) expression to increase neuronal cell damage. Furthermore, circ_0000018 knockdown significantly improved neuronal cell viability and attenuated OGD/R‑treated neuronal cell death. Meanwhile, circ_0000018 knockdown improved brain infarct volume and neuronal apoptosis in tMCAO mice. The present study found that circ_0000018 knockdown relieved cerebral ischemia‑reperfusion injury progression in vitro and in vivo. Mechanistically, circ_0000018 regulated the levels of BCL2L11 by sponging miR‑871.

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1	Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL and Parag V: Worldwide stroke incidence and early case fatality reported in 56 population-based studies: A systematic review. Lancet Neurol. 8:355–369. 2009. View Article : Google Scholar : PubMed/NCBI
2	Inohara T, Liang L, Kosinski AS, Smith EE, Schwamm LH, Hernandez AF, Bhatt DL, Fonarow GC, Peterson ED and Xian Y: Recent myocardial infarction is associated with increased risk in older adults with acute ischemic stroke receiving thrombolytic therapy. J Am Heart Assoc. 8:e0124502019. View Article : Google Scholar : PubMed/NCBI
3	Wang YJ, Li ZX, Gu HQ, Zhai Y, Jiang Y, Zhao XQ, Wang YL, Yang X, Wang CJ, Meng X, et al: China stroke statistics 2019: A report from the national center for healthcare quality management in neurological diseases, China national clinical research center for neurological diseases, the Chinese stroke association, national center for chronic and non-communicable disease control and prevention, Chinese center for disease control and prevention and institute for global neuroscience and stroke collaborations. Stroke Vasc Neurol. 5:211–239. 2020. View Article : Google Scholar : PubMed/NCBI
4	GBD 2019 Stroke Collaborators, . Global, regional, and national burden of stroke and its risk factors, 1990–2019: A systematic analysis for the global burden of disease study 2019. Lancet Neurol. 20:795–820. 2021. View Article : Google Scholar : PubMed/NCBI
5	Chen Z, Jiang B, Ru X, Sun H, Sun D, Liu X, Li Y, Li D, Guo X and Wang W: Mortality of stroke and its subtypes in China: Results from a nationwide population-based survey. Neuroepidemiology. 48:95–102. 2017. View Article : Google Scholar : PubMed/NCBI
6	Jeck WR and Sharpless NE: Detecting and characterizing circular RNAs. Nat Biotechnol. 32:453–461. 2014. View Article : Google Scholar : PubMed/NCBI
7	Ebbesen KK, Kjems J and Hansen TB: Circular RNAs: Identification, biogenesis and function. Biochim Biophys Acta. 1859:163–168. 2016. View Article : Google Scholar : PubMed/NCBI
8	Ostolaza A, Blanco-Luquin I, Urdánoz-Casado A, Rubio I, Labarga A, Zandio B, Roldán M, Martínez-Cascales J, Mayor S, Herrera M, et al: Circular RNA expression profile in blood according to ischemic stroke etiology. Cell Biosci. 10:342020. View Article : Google Scholar : PubMed/NCBI
9	Wu F, Han B, Wu S, Yang L, Leng S, Li M, Liao J, Wang G, Ye Q, Zhang Y, et al: Circular RNA TLK1 aggravates neuronal injury and neurological deficits after ischemic stroke via miR-335-3p/TIPARP. J Neurosci. 39:7369–7393. 2019. View Article : Google Scholar : PubMed/NCBI
10	Peng X, Jing P, Chen J and Xu L: The role of circular RNA HECTD1 expression in disease risk, disease severity, inflammation, and recurrence of acute ischemic stroke. J Clin Lab Anal. 33:e229542019. View Article : Google Scholar : PubMed/NCBI
11	Van Rooij E, Purcell AL and Levin AA: Developing micro RNA therapeutics. Circ Res. 110:496–507. 2012. View Article : Google Scholar : PubMed/NCBI
12	Ghoreishy A, Khosravi A and Ghaemmaghami A: Exosomal microRNA and stroke: A review. J Cell Biochem. 120:16352–16361. 2019. View Article : Google Scholar : PubMed/NCBI
13	Chen Y, Gao C, Sun Q, Pan H, Huang P, Ding J and Chen S: MicroRNA-4639 is a regulator of DJ-1 expression and a potential early diagnostic marker for Parkinson's disease. Front Aging Neurosci. 9:2322017. View Article : Google Scholar : PubMed/NCBI
14	Arena A, Iyer AM, Milenkovic I, Kovacs GG, Ferrer I, Perluigi M and Aronica E: Developmental expression and dysregulation of miR-146a and miR-155 in Down's syndrome and mouse models of Down's syndrome and Alzheimer's disease. Curr Alzheimer Res. 14:1305–1317. 2017. View Article : Google Scholar : PubMed/NCBI
15	Beveridge NJ, Tooney PA, Carroll AP, Gardiner E, Bowden N, Scott RJ, Tran N, Dedova I and Cairns MJ: Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. Hum Mol Genet. 17:1156–1168. 2008. View Article : Google Scholar : PubMed/NCBI
16	Jeyaseelan K, Lim KY and Armugam A: MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke. 39:959–966. 2008. View Article : Google Scholar : PubMed/NCBI
17	Dharap A, Bowen K, Place R, Li LC and Vemuganti R: Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome. J Cereb Blood Flow Metab. 29:675–687. 2009. View Article : Google Scholar : PubMed/NCBI
18	Liu DZ, Tian Y, Ander BP, Xu H, Stamova BS, Zhan X, Turner RJ, Jickling G and Sharp FR: Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures. J Cereb Blood Flow Metab. 30:92–101. 2010. View Article : Google Scholar : PubMed/NCBI
19	Abe A, Tanaka M, Yasuoka A, Saito Y, Okada S, Mishina M, Abe K, Kimura K and Asakura T: Changes in whole-blood microRNA profiles during the onset and treatment process of cerebral infarction: A human study. Int J Mol Sci. 21:31072020. View Article : Google Scholar : PubMed/NCBI
20	Han B, Zhang Y, Zhang Y, Bai Y, Chen X, Huang R, Wu F, Leng S, Chao J, Zhang JH, et al: Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142-TIPARP: Implications for cerebral ischemic stroke. Autophagy. 14:1164–1184. 2018. View Article : Google Scholar : PubMed/NCBI
21	R Core Team, . R: A language and environment for statistical computing. R Foundation for Statistical Computing; Vienna, Austria: ISBN 3-900051-07-0. 2012
22	RStudio Team, . Rstudio: Integrated development for R. Rstudio Inc.; Boston, MA: 2015
23	Liu W, Miao Y, Zhang L, Xu X and Luan Q: MiR-211 protects cerebral ischemia/reperfusion injury by inhibiting cell apoptosis. Bioengineered. 11:189–200. 2020. View Article : Google Scholar : PubMed/NCBI
24	Wibrand K, Pai Bl, Siripornmongcolchai T, Bittins M, Berentsen B, Ofte ML, Weigel A, Skaftnesmo KO and Bramham CR: MicroRNA regulation of the synaptic plasticity-related gene Arc. PLoS One. 7:e416882012. View Article : Google Scholar : PubMed/NCBI
25	Fiore R, Khudayberdiev S, Christensen M, Siegel G, Flavell SW, Kim TK, Greenberg ME and Schratt G: Mef2-mediated transcription of the miR379-410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels. EMBO J. 28:697–710. 2009. View Article : Google Scholar : PubMed/NCBI
26	Magill ST, Cambronne XA, Luikart BW, Lioy DT, Leighton BH, Westbrook GL, Mandel G and Goodman RH: microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus. Proc Natl Acad Sci USA. 107:20382–20387. 2010. View Article : Google Scholar : PubMed/NCBI
27	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
28	Olde Loohuis NFM, Kos A, Martens GJM, Van Bokhoven H, Nadif Kasri N and Aschrafi A: MicroRNA networks direct neuronal development and plasticity. Cell Mol Life Sci. 69:89–102. 2012. View Article : Google Scholar : PubMed/NCBI
29	Broderick JA and Zamore PD: MicroRNA therapeutics. Gene Ther. 18:1104–1110. 2011. View Article : Google Scholar : PubMed/NCBI
30	Hu J, Xie C, Xu S, Pu Q, Liu H, Yang L, Wang W, Mao L, Li Z and Chen W: Liver fibrosis-derived exosomal miR-106a-5p facilitates the malignancy by targeting SAMD12 and CADM2 in hepatocellular carcinoma. PLoS One. 18:e02860172023. View Article : Google Scholar : PubMed/NCBI
31	Tuo X, Zhou Y, Yang X, Ma S, Liu D, Zhang X, Hou H, Wang R, Li X and Zhao L: miR-532-3p suppresses proliferation and invasion of ovarian cancer cells via GPNMB/HIF-1α/HK2 axis. Pathol Res Pract. 237:1540322022. View Article : Google Scholar : PubMed/NCBI
32	Cheng Q, Chen M, Wang H, Chen X, Wu H, Du Y and Xue J: MicroRNA-27a-3p inhibits lung and skin fibrosis of systemic sclerosis by negatively regulating SPP1. Genomics. 114:1103912022. View Article : Google Scholar : PubMed/NCBI
33	Mehta SL, Pandi G and Vemuganti R: Circular RNA expression profiles alter significantly in mouse brain after transient focal ischemia. Stroke. 48:2541–2548. 2017. View Article : Google Scholar : PubMed/NCBI
34	Liu C, Zhang C, Yang J, Geng X, Du H, Ji X and Zhao H: Screening circular RNA expression patterns following focal cerebral ischemia in mice. Oncotarget. 8:86535–86547. 2017. View Article : Google Scholar : PubMed/NCBI
35	Duan X, Li L, Gan J, Peng C, Wang X, Chen W and Peng D: Identification and functional analysis of circular RNAs induced in rats by middle cerebral artery occlusion. Gene. 701:139–145. 2019. View Article : Google Scholar : PubMed/NCBI
36	Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK and Kjems J: Natural RNA circles function as efficient microRNA sponges. Nature. 495:384–388. 2013. View Article : Google Scholar : PubMed/NCBI
37	Dai Q, Ma Y, Xu Z, Zhang L, Yang H, Liu Q and Wang J: Downregulation of circular RNA HECTD1 induces neuroprotection against ischemic stroke through the microRNA-133b/TRAF3 pathway. Life Sci. 264:1186262021. View Article : Google Scholar : PubMed/NCBI
38	Pei L, Xu X and Yuan T: Circ_0101874 overexpression strengthens PDE4D expression by targeting miR-335-5p to promote neuronal injury in ischemic stroke. J Stroke Cerebrovasc Dis. 31:1068172022. View Article : Google Scholar : PubMed/NCBI
39	Zhang Z, He J and Wang B: Circular RNA circ_HECTD1 regulates cell injury after cerebral infarction by miR-27a-3p/FSTL1 axis. Cell Cycle. 20:914–926. 2021. View Article : Google Scholar : PubMed/NCBI
40	Concannon CG, Tuffy LP, Weisová P, Bonner HP, Dávila D, Bonner C, Devocelle MC, Strasser A, Ward MW and Prehn JH: AMP kinase-mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis. Cell Biol. 189:83–94. 2010. View Article : Google Scholar : PubMed/NCBI
41	Kilbride SM, Farrelly AM, Bonner C, Ward MW, Nyhan KC, Concannon CG, Wollheim CB, Byrne MM and Prehn JH: AMP-activated protein kinase mediates apoptosis in response to bioenergetic stress through activation of the pro-apoptotic Bcl-2 homology domain-3-only protein BMF. J Biol Chem. 285:36199–36206. 2010. View Article : Google Scholar : PubMed/NCBI
42	Ouyang YB, Xu L, Lu Y, Sun X, Yue S, Xiong XX and Giffard RG: Astrocyte-enriched miR-29a targets PUMA and reduces neuronal vulnerability to forebrain ischemia. Glia. 61:1784–1794. 2013. View Article : Google Scholar : PubMed/NCBI
43	Liu L, Liu Y, Zhang T, Wu H, Lin M, Wang C, Zhan Y, Zhou Q, Qiao B, Sun X, et al: Synthetic Bax-Anti Bcl2 combination module actuated by super artificial hTERT promoter selectively inhibits malignant phenotypes of bladder cancer. Exp Clin Cancer Res. 35:32016. View Article : Google Scholar : PubMed/NCBI
44	Strasser A: The role of BH3-only proteins in the immune system. Nat Rev Immunol. 5:189–200. 2005. View Article : Google Scholar : PubMed/NCBI
45	Chen S, Wang M, Yang H, Mao L, He Q, Jin H, Ye ZM, Luo XY, Xia YP and Hu B: LncRNA TUG1 sponges microRNA-9 to promote neurons apoptosis by up-regulated Bcl2l11 under ischemia. Biochem Biophys Res Commun. 485:167–173. 2017. View Article : Google Scholar : PubMed/NCBI