miR-135b levels in the peripheral blood serve as a marker associated with acute ischemic stroke

Yang,Sha; Zhan,Xinyu; He,Min; Wang,Jingjing; Qiu,Xuemei

doi:10.3892/etm.2020.8628

miR-135b levels in the peripheral blood serve as a marker associated with acute ischemic stroke

Authors:
- Sha Yang
- Xinyu Zhan
- Min He
- Jingjing Wang
- Xuemei Qiu
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Affiliations: Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China, Vasculocardiology Department, The 903rd Hospital of PLA, Hangzhou, Zhejiang 310013, P.R. China, Department of Clinical Laboratory Medicine, The 80th Army Hospital of PLA, Weifang, Shandong 261021, P.R. China
Published online on: March 30, 2020 https://doi.org/10.3892/etm.2020.8628
Pages: 3551-3558
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The protective role of microRNA (miR)-135b in cerebral neurons has been previously identified. However, to the best of our knowledge, the involvement of miR-135b in acute ischemic stroke has yet to be elucidated. The present study aimed to investigate the expression profile of miR-135b in peripheral blood obtained from patients with acute ischemic stroke. A total of 76 patients with acute ischemic stroke were selected as the case group, which included 33 cases of aorta atheromatous plague, 19 cases of cardioembolism, 16 cases of small arterial occlusion and 8 cases with unknown causes. In addition, 60 healthy subjects were selected as the control group. Reverse transcription-quantitative PCR was used to measure the expression of miR-135b in the peripheral blood of the patients. The National Institutes of Health Stroke Scale (NIHSS) score was used to evaluate the severity of acute ischemic stroke. The relationship between miR-135b levels and acute stroke was subsequently analyzed. The expression of miR-135b in the peripheral blood of the case group was found to be significantly higher compared with that in the control group. By contrast, the expression levels of miR-135b in the case group did not differ significantly between the different etiology types of acute ischemic stroke. In addition, a significant positive correlation was observed between levels of miR-135b expression and NIHSS scores. Further analysis demonstrated that hypertension, hyperglycemia, platelet count, international normalized ratio and miR-135b were risk factors for acute ischemic stroke. Based on bioinformatics analysis, a conserved binding site for miR-135b was identified in the 3'-untranslated region of the transient receptor potential cation channel subfamily C member 6 (TRPC6). Dual luciferase reporter and western blot analysis showed that TRPC6 was a target gene of miR-135b. In conclusion, data from the present study suggest that elevated expression of miR-135b in the peripheral blood of patients with acute ischemic stroke is closely associated with disease severity.

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1	Du K, Zhao C, Wang L, Wang Y, Zhang KZ, Shen XY, Sun HX, Gao W and Lu X: MiR-191 inhibit angiogenesis after acute ischemic stroke targeting VEZF1. Aging (Albany NY). 11:2762–2786. 2019.PubMed/NCBI View Article : Google Scholar
2	Chen Z, Wang K, Huang J, Zheng G, Lv Y, Luo N, Liang M and Huang L: Upregulated serum MiR-146b serves as a biomarker for acute ischemic stroke. Cell Physiol Biochem. 45:397–405. 2018.PubMed/NCBI View Article : Google Scholar
3	Marquez-Romero JM, Góngora-Rivera F, Hernández-Curiel BC, Aburto-Murrieta Y, García-Cazares R, Delgado-Garzón P, Murillo-Bonilla LM and Ochoa-Solórzano MA: Endovascular treatment of ischemic stroke in a developing country. Vasc Endovascular Surg: Feb 19, 2020 (Epub ahead of print).
4	Béjot Y, Daubail B and Giroud M: Epidemiology of stroke and transient ischemic attacks: Current knowledge and perspectives. Rev Neurol (Paris). 172:59–68. 2016.PubMed/NCBI View Article : Google Scholar
5	Cheng X, Kan P, Ma Z, Wang Y, Song W, Huang C and Zhang B: Exploring the potential value of miR-148b-3p, miR-151b and miR-27b-3p as biomarkers in acute ischemic stroke. Biosci Rep. 38(38)2018.PubMed/NCBI View Article : Google Scholar
6	Ji Q, Ji Y, Peng J, Zhou X, Chen X, Zhao H, Xu T, Chen L and Xu Y: Increased brain-specific MiR-9 and MiR-124 in the serum exosomes of acute ischemic stroke patients. PLoS One. 11(e0163645)2016.PubMed/NCBI View Article : Google Scholar
7	Jia L, Hao F, Wang W and Qu Y: Circulating miR-145 is associated with plasma high-sensitivity C-reactive protein in acute ischemic stroke patients. Cell Biochem Funct. 33:314–319. 2015.PubMed/NCBI View Article : Google Scholar
8	Jiang M, Wang H, Jin M, Yang X, Ji H, Jiang Y, Zhang H, Wu F, Wu G, Lai X, et al: Exosomes from MiR-30d-5p-ADSCs reverse acute ischemic stroke-induced, autophagy-mediated brain injury by promoting M2 microglial/macrophage polarization. Cell Physiol Biochem. 47:864–878. 2018.PubMed/NCBI View Article : Google Scholar
9	Jin F and Xing J: Circulating miR-126 and miR-130a levels correlate with lower disease risk, disease severity, and reduced inflammatory cytokine levels in acute ischemic stroke patients. Neurol Sci. 39:1757–1765. 2018.PubMed/NCBI View Article : Google Scholar
10	Khanna S, Rink C, Ghoorkhanian R, Gnyawali S, Heigel M, Wijesinghe DS, Chalfant CE, Chan YC, Banerjee J, Huang Y, et al: Loss of miR-29b following acute ischemic stroke contributes to neural cell death and infarct size. J Cereb Blood Flow Metab. 33:1197–1206. 2013.PubMed/NCBI View Article : Google Scholar
11	Li SH, Chen L, Pang XM, Su SY, Zhou X, Chen CY, Huang LG, Li JP and Liu JL: Decreased miR-146a expression in acute ischemic stroke directly targets the Fbxl10 mRNA and is involved in modulating apoptosis. Neurochem Int. 107:156–167. 2017.PubMed/NCBI View Article : Google Scholar
12	Su ZF, Sun ZW, Zhang Y, Wang S, Yu QG and Wu ZB: Regulatory effects of miR-146a/b on the function of endothelial progenitor cells in acute ischemic stroke in mice. Kaohsiung J Med Sci. 33:369–378. 2017.PubMed/NCBI View Article : Google Scholar
13	Tiedt S, Prestel M, Malik R, Schieferdecker N, Duering M, Kautzky V, Stoycheva I, Böck J, Northoff BH, Klein M, et al: RNA-Seq identifies circulating miR-125a-5p, miR-125b-5p, and miR-143-3p as potential biomarkers for acute ischemic stroke. Circ Res. 121:970–980. 2017.PubMed/NCBI View Article : Google Scholar
14	Wang Y, Zhang Y, Huang J, Chen X, Gu X, Wang Y, Zeng L and Yang GY: Increase of circulating miR-223 and insulin-like growth factor-1 is associated with the pathogenesis of acute ischemic stroke in patients. BMC Neurol. 14(77)2014.PubMed/NCBI View Article : Google Scholar
15	Wu J, Du K and Lu X: Elevated expressions of serum miR-15a, miR-16, and miR-17-5p are associated with acute ischemic stroke. Int J Clin Exp Med. 8:21071–21079. 2015.PubMed/NCBI
16	Zhang J, Liu W, Wang Y, Zhao S and Chang N: miR-135b plays a neuroprotective role by targeting GSK3β in MPP⁺-intoxicated SH-SY5Y Cells. Dis Markers. 2017(5806146)2017.PubMed/NCBI View Article : Google Scholar
17	Sillivan SE, Jamieson S, de Nijs L, Jones M, Snidjers C, Klengel T, Joseph NF, Krauskopf J, Kleinjans J and Vinkers CH: MicroRNA regulation of persistent stress-enhanced memory. Mol Psychiatry: May 29, 2019 (Epub ahead of print).
18	Jiang B, Ball RL, Michel P, Jovin T, Desai M, Eskandari A, Naqvi Z and Wintermark M: Prevalence of imaging biomarkers to guide the planning of acute stroke reperfusion trials. Stroke. 48:1675–1677. 2017.PubMed/NCBI View Article : Google Scholar
19	Kwah LK and Diong J: National Institutes of Health Stroke Scale (NIHSS). J Physiother. 60(61)2014.PubMed/NCBI View Article : Google Scholar
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^-^ΔΔ^CT Method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
21	Yang X, Liu Y, Liu C, Xie W, Huang E, Huang W, Wang J, Chen L, Wang H, Qiu P, et al: Inhibition of ROCK2 expression protects against methamphetamine-induced neurotoxicity in PC12 cells. Brain Res. 1533:16–25. 2013.PubMed/NCBI View Article : Google Scholar
22	Rong F, Gao X, Liu K and Wu J: Methotrexate remediates spinal cord injury in vivo and in vitro via suppression of endoplasmic reticulum stress-induced apoptosis. Exp Ther Med. 15:4191–4198. 2018.PubMed/NCBI View Article : Google Scholar
23	Xiang W, Tian C, Lin J, Wu X, Pang G, Zhou L, Pan S and Deng Z: Plasma let-7i and miR-15a expression are associated with the effect of recombinant tissue plasminogen activator treatment in acute ischemic stroke patients. Thromb Res. 158:121–125. 2017.PubMed/NCBI View Article : Google Scholar
24	Zhao B, Zhu Z, Hao J, Wan Z and Guo X: Decreased plasma miR-335 expression in patients with acute ischemic stroke and its association with calmodulin expression. J Int Med Res. 44:1331–1338. 2016.PubMed/NCBI View Article : Google Scholar
25	Zhou J, Chen L, Chen B, Huang S, Zeng C, Wu H, Chen C and Long F: Increased serum exosomal miR-134 expression in the acute ischemic stroke patients. BMC Neurol. 18(198)2018.PubMed/NCBI View Article : Google Scholar
26	Ko Y, Lee S, Chung JW, Han MK, Park JM, Kang K, Park TH, Park SS, Cho YJ, Hong KS, et al: MRI-based algorithm for acute ischemic stroke subtype classification. J Stroke. 16:161–172. 2014.PubMed/NCBI View Article : Google Scholar
27	Shi FP, Wang XH, Zhang HX, Shang MM, Liu XX, Sun HM and Song YP: MiR-103 regulates the angiogenesis of ischemic stroke rats by targeting vascular endothelial growth factor (VEGF). Iran J Basic Med Sci. 21:318–324. 2018.PubMed/NCBI View Article : Google Scholar
28	Yao S, Tang B, Li G, Fan R and Cao F: miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke. Neuropsychiatr Dis Treat. 12:3083–3092. 2016.PubMed/NCBI View Article : Google Scholar
29	Wang J, Lin M, Ren H, Yu Z, Guo T and Gu B: Expression and clinical significance of serum miR-497 in patients with acute cerebral infarction. Clin Lab. 65(65)2019.PubMed/NCBI View Article : Google Scholar
30	Cojocaru IM, Cojocaru M, Tănăsescu R, Iliescu I, Dumitrescu L and Silosi I: Expression of IL-6 activity in patients with acute ischemic stroke. Rom J Intern Med. 47:393–396. 2009.PubMed/NCBI
31	Kwan J, Horsfield G, Bryant T, Gawne-Cain M, Durward G, Byrne CD and Englyst NA: IL-6 is a predictive biomarker for stroke associated infection and future mortality in the elderly after an ischemic stroke. Exp Gerontol. 48:960–965. 2013.PubMed/NCBI View Article : Google Scholar
32	Griesi-Oliveira K, Acab A, Gupta AR, Sunaga DY, Chailangkarn T, Nicol X, Nunez Y, Walker MF, Murdoch JD, Sanders SJ, et al: Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons. Mol Psychiatry. 20:1350–1365. 2015.PubMed/NCBI View Article : Google Scholar
33	Li W, Yang F, Gao J, Tang Y, Wang J and Pan Y: Over-expression of TRPC6 via CRISPR based synergistic activation mediator in BMSCs ameliorates brain injury in a rat model of cerebral ischemia/reperfusion. Neuroscience. 415:147–160. 2019.PubMed/NCBI View Article : Google Scholar
34	Li H, Huang J, Du W, Jia C, Yao H and Wang Y: TRPC6 inhibited NMDA receptor activities and protected neurons from ischemic excitotoxicity. J Neurochem. 123:1010–1018. 2012.PubMed/NCBI View Article : Google Scholar
35	Du W, Huang J, Yao H, Zhou K, Duan B and Wang Y: Inhibition of TRPC6 degradation suppresses ischemic brain damage in rats. J Clin Invest. 120:3480–3492. 2010.PubMed/NCBI View Article : Google Scholar
36	Guo C, Ma Y, Ma S, Mu F, Deng J, Duan J, Xiong L, Yin Y, Wang Y, Xi M, et al: The role of TRPC6 in the neuroprotection of calycosin against cerebral ischemic injury. Sci Rep. 7(3039)2017.PubMed/NCBI View Article : Google Scholar