Skip to main content
Top
Published in: BMC Neurology 1/2013

Open Access 01-12-2013 | Research article

Circulating miR-30a, miR-126 and let-7b as biomarker for ischemic stroke in humans

Authors: Guangwen Long, Feng Wang, Huaping Li, Zhongwei Yin, Chaugai Sandip, Yan Lou, Yan Wang, Chen Chen, Dao Wen Wang

Published in: BMC Neurology | Issue 1/2013

Login to get access

Abstract

Background

Recently, plasma miRNAs have been reported as biomarkers for various diseases. However, the knowledge on the association of plasma miRNAs with ischemic stroke is still lacking. In this study, we investigated whether plasma concentrations of miR-30a, miR-126 and let-7b may be biomarkers for ischemic stroke in humans.

Methods

One hundred ninety seven patients with ischemic stroke were recruited and their blood samples were collected at 24 h, 1 week, 4 weeks, 24 weeks and 48 weeks after symptoms onset, and fifty healthy volunteers were selected as control. Levels of miRNA were quantified by quantitative real-time PCR. Relative expression level of miRNA was calculated using 2-ΔΔct method. The ability to distinguish the ischemic stroke group from control group was characterized by receiver operating characteristic (ROC) curve, and the area under ROC curve (AUC) was calculated.

Results

Circulating miR-30a and miR-126 levels were markedly down-regulated in all patients with ischemic stroke until 24 weeks. However, circulating let-7b was lower in patients with large-vessel atherosclerosis than healthy volunteers, whereas circulating let-7b had higher level in patients with other kinds of ischemic stroke until 24 weeks. Among all patients, circulating miRNAs levels returned to normal 48 weeks after symptom onset. Receiver operating characteristic (ROC) curve analysis showed that the areas under the curve (AUC) of plasma miR-30a were 0.91, 0.91, 0.92 and 0.93, the miR-126 were 0.92, 0.94, 0.93 and 0.92, and let-7b were 0.93, 0.92, 0.92 and 0.91 at 24 h, 1 w, 4 w and 24 w, respectively.

Conclusions

These data suggest that miR-30a, miR-126 and let-7b might be useful biomarkers for ischemic stroke in humans.
Appendix
Available only for authorised users
Literature
1.
go back to reference Goldstein LB, Adams R, Becker K, Furberg CD, Gorelick PB, Hademenos G, Hill M, Howard G, Howard VJ, Jacobs B, et al: Primary prevention of ischemic stroke: a statement for healthcare professionals from the stroke council of the American heart association. Stroke. 2001, 32 (1): 280-299. 10.1161/01.STR.32.1.280.CrossRefPubMed Goldstein LB, Adams R, Becker K, Furberg CD, Gorelick PB, Hademenos G, Hill M, Howard G, Howard VJ, Jacobs B, et al: Primary prevention of ischemic stroke: a statement for healthcare professionals from the stroke council of the American heart association. Stroke. 2001, 32 (1): 280-299. 10.1161/01.STR.32.1.280.CrossRefPubMed
2.
go back to reference Liu L, Wang D, Wong KS, Wang Y: Stroke and stroke care in China: huge burden, significant workload, and a national priority. Stroke. 2011, 42 (12): 3651-3654. 10.1161/STROKEAHA.111.635755.CrossRefPubMed Liu L, Wang D, Wong KS, Wang Y: Stroke and stroke care in China: huge burden, significant workload, and a national priority. Stroke. 2011, 42 (12): 3651-3654. 10.1161/STROKEAHA.111.635755.CrossRefPubMed
3.
go back to reference Prugger C, Luc G, Haas B, Morange PE, Ferrieres J, Amouyel P, Kee F, Ducimetiere P, Empana JP, on behalf of the PSG: Multiple biomarkers for the prediction of ischemic stroke: the PRIME study. Arterioscler Thromb Vasc Biol. 2013, 3 (3): 659-666.CrossRef Prugger C, Luc G, Haas B, Morange PE, Ferrieres J, Amouyel P, Kee F, Ducimetiere P, Empana JP, on behalf of the PSG: Multiple biomarkers for the prediction of ischemic stroke: the PRIME study. Arterioscler Thromb Vasc Biol. 2013, 3 (3): 659-666.CrossRef
4.
go back to reference Guo H, Ingolia NT, Weissman JS, Bartel DP: Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010, 466 (7308): 835-840. 10.1038/nature09267.CrossRefPubMedPubMedCentral Guo H, Ingolia NT, Weissman JS, Bartel DP: Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010, 466 (7308): 835-840. 10.1038/nature09267.CrossRefPubMedPubMedCentral
5.
6.
go back to reference van Rooij E, Olson EN: MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nature reviews Drug discovery. 2012, 11 (11): 860-872. 10.1038/nrd3864.CrossRefPubMed van Rooij E, Olson EN: MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nature reviews Drug discovery. 2012, 11 (11): 860-872. 10.1038/nrd3864.CrossRefPubMed
7.
go back to reference Frankel LB, Lund AH: MicroRNA regulation of autophagy. Carcinogenesis. 2012, 33 (11): 2018-2025. 10.1093/carcin/bgs266.CrossRefPubMed Frankel LB, Lund AH: MicroRNA regulation of autophagy. Carcinogenesis. 2012, 33 (11): 2018-2025. 10.1093/carcin/bgs266.CrossRefPubMed
8.
go back to reference Zampetaki A, Mayr M: MicroRNAs in vascular and metabolic disease. Circulation research. 2012, 110 (3): 508-522. 10.1161/CIRCRESAHA.111.247445.CrossRefPubMed Zampetaki A, Mayr M: MicroRNAs in vascular and metabolic disease. Circulation research. 2012, 110 (3): 508-522. 10.1161/CIRCRESAHA.111.247445.CrossRefPubMed
10.
go back to reference Ruberti F, Barbato C, Cogoni C: Targeting microRNAs in neurons: tools and perspectives. Experimental neurology. 2012, 235 (2): 419-426. 10.1016/j.expneurol.2011.10.031.CrossRefPubMed Ruberti F, Barbato C, Cogoni C: Targeting microRNAs in neurons: tools and perspectives. Experimental neurology. 2012, 235 (2): 419-426. 10.1016/j.expneurol.2011.10.031.CrossRefPubMed
11.
go back to reference Kosik KS: The neuronal microRNA system. Nature reviews Neuroscience. 2006, 7 (12): 911-920. 10.1038/nrn2037.CrossRefPubMed Kosik KS: The neuronal microRNA system. Nature reviews Neuroscience. 2006, 7 (12): 911-920. 10.1038/nrn2037.CrossRefPubMed
12.
go back to reference Karres JS, Hilgers V, Carrera I, Treisman J, Cohen SM: The conserved microRNA miR-8 tunes atrophin levels to prevent neurodegeneration in Drosophila. Cell. 2007, 131 (1): 136-145. 10.1016/j.cell.2007.09.020.CrossRefPubMed Karres JS, Hilgers V, Carrera I, Treisman J, Cohen SM: The conserved microRNA miR-8 tunes atrophin levels to prevent neurodegeneration in Drosophila. Cell. 2007, 131 (1): 136-145. 10.1016/j.cell.2007.09.020.CrossRefPubMed
13.
go back to reference Jeon YJ, Kim OJ, Kim SY, Oh SH, Oh D, Kim OJ, Shin BS, Kim NK: Association of the miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms with ischemic stroke and silent brain infarction risk. Arteriosclerosis, thrombosis, and vascular biology. 2013, 33 (2): 420-430. 10.1161/ATVBAHA.112.300251.CrossRefPubMed Jeon YJ, Kim OJ, Kim SY, Oh SH, Oh D, Kim OJ, Shin BS, Kim NK: Association of the miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms with ischemic stroke and silent brain infarction risk. Arteriosclerosis, thrombosis, and vascular biology. 2013, 33 (2): 420-430. 10.1161/ATVBAHA.112.300251.CrossRefPubMed
14.
go back to reference Ai J, Sun LH, Che H, Zhang R, Zhang TZ, Wu WC, Su XL, Chen X, Yang G, Li K, et al: MicroRNA-195 protects against dementia induced by chronic brain hypoperfusion via its anti-amyloidogenic effect in rats. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2013, 33 (9): 3989-4001. 10.1523/JNEUROSCI.1997-12.2013.CrossRef Ai J, Sun LH, Che H, Zhang R, Zhang TZ, Wu WC, Su XL, Chen X, Yang G, Li K, et al: MicroRNA-195 protects against dementia induced by chronic brain hypoperfusion via its anti-amyloidogenic effect in rats. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2013, 33 (9): 3989-4001. 10.1523/JNEUROSCI.1997-12.2013.CrossRef
15.
go back to reference Jeyaseelan K, Lim KY, Armugam A: MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke. 2008, 39 (3): 959-966. 10.1161/STROKEAHA.107.500736.CrossRefPubMed Jeyaseelan K, Lim KY, Armugam A: MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke. 2008, 39 (3): 959-966. 10.1161/STROKEAHA.107.500736.CrossRefPubMed
16.
go back to reference Bridge G, Monteiro R, Henderson S, Emuss V, Lagos D, Georgopoulou D, Patient R, Boshoff C: The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis. Blood. 2012, 120 (25): 5063-5072. 10.1182/blood-2012-04-423004.CrossRefPubMed Bridge G, Monteiro R, Henderson S, Emuss V, Lagos D, Georgopoulou D, Patient R, Boshoff C: The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis. Blood. 2012, 120 (25): 5063-5072. 10.1182/blood-2012-04-423004.CrossRefPubMed
17.
go back to reference Tan KS, Armugam A, Sepramaniam S, Lim KY, Setyowati KD, Wang CW, Jeyaseelan K: Expression profile of MicroRNAs in young stroke patients. PloS one. 2009, 4 (11): e7689-10.1371/journal.pone.0007689.CrossRefPubMedPubMedCentral Tan KS, Armugam A, Sepramaniam S, Lim KY, Setyowati KD, Wang CW, Jeyaseelan K: Expression profile of MicroRNAs in young stroke patients. PloS one. 2009, 4 (11): e7689-10.1371/journal.pone.0007689.CrossRefPubMedPubMedCentral
18.
go back to reference Diskin SJ, Capasso M, Schnepp RW, Cole KA, Attiyeh EF, Hou C, Diamond M, Carpenter EL, Winter C, Lee H, et al: Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma. Nature genetics. 2012, 44 (10): 1126-1130. 10.1038/ng.2387.CrossRefPubMedPubMedCentral Diskin SJ, Capasso M, Schnepp RW, Cole KA, Attiyeh EF, Hou C, Diamond M, Carpenter EL, Winter C, Lee H, et al: Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma. Nature genetics. 2012, 44 (10): 1126-1130. 10.1038/ng.2387.CrossRefPubMedPubMedCentral
19.
go back to reference Lehmann SM, Kruger C, Park B, Derkow K, Rosenberger K, Baumgart J, Trimbuch T, Eom G, Hinz M, Kaul D, et al: An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration. Nature neuroscience. 2012, 15 (6): 827-835. 10.1038/nn.3113.CrossRefPubMed Lehmann SM, Kruger C, Park B, Derkow K, Rosenberger K, Baumgart J, Trimbuch T, Eom G, Hinz M, Kaul D, et al: An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration. Nature neuroscience. 2012, 15 (6): 827-835. 10.1038/nn.3113.CrossRefPubMed
20.
go back to reference Wang F, Long G, Zhao C, Li H, Chaugai S, Wang Y, Chen C, Wang DW: Plasma microRNA-133a is a new marker for both acute myocardial infarction and underlying coronary artery stenosis. Journal of translational medicine. 2013, 11 (1): 222-10.1186/1479-5876-11-222.CrossRefPubMedPubMedCentral Wang F, Long G, Zhao C, Li H, Chaugai S, Wang Y, Chen C, Wang DW: Plasma microRNA-133a is a new marker for both acute myocardial infarction and underlying coronary artery stenosis. Journal of translational medicine. 2013, 11 (1): 222-10.1186/1479-5876-11-222.CrossRefPubMedPubMedCentral
21.
go back to reference Long G, Wang F, Duan Q, Yang S, Chen F, Gong W, Yang X, Wang Y, Chen C, Wang DW: Circulating miR-30a, miR-195 and let-7b associated with acute myocardial infarction. PloS one. 2012, 7 (12): e50926-10.1371/journal.pone.0050926.CrossRefPubMedPubMedCentral Long G, Wang F, Duan Q, Yang S, Chen F, Gong W, Yang X, Wang Y, Chen C, Wang DW: Circulating miR-30a, miR-195 and let-7b associated with acute myocardial infarction. PloS one. 2012, 7 (12): e50926-10.1371/journal.pone.0050926.CrossRefPubMedPubMedCentral
22.
go back to reference Long G, Wang F, Duan Q, Chen F, Yang S, Gong W, Wang Y, Chen C, Wang DW: Human circulating microRNA-1 and microRNA-126 as potential novel indicators for acute myocardial infarction. International journal of biological sciences. 2012, 8 (6): 811-818.CrossRefPubMedPubMedCentral Long G, Wang F, Duan Q, Chen F, Yang S, Gong W, Wang Y, Chen C, Wang DW: Human circulating microRNA-1 and microRNA-126 as potential novel indicators for acute myocardial infarction. International journal of biological sciences. 2012, 8 (6): 811-818.CrossRefPubMedPubMedCentral
23.
go back to reference Zhang Q, Ding H, Yan J, Wang W, Ma A, Zhu Z, Cianflone K, Hu FB, Hui R, Wang DW: Plasma tissue kallikrein level is negatively associated with incident and recurrent stroke: a multicenter case–control study in China. Annals of neurology. 2011, 70 (2): 265-273. 10.1002/ana.22404.CrossRefPubMed Zhang Q, Ding H, Yan J, Wang W, Ma A, Zhu Z, Cianflone K, Hu FB, Hui R, Wang DW: Plasma tissue kallikrein level is negatively associated with incident and recurrent stroke: a multicenter case–control study in China. Annals of neurology. 2011, 70 (2): 265-273. 10.1002/ana.22404.CrossRefPubMed
24.
go back to reference Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001, 25 (4): 402-408. 10.1006/meth.2001.1262.CrossRefPubMed Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001, 25 (4): 402-408. 10.1006/meth.2001.1262.CrossRefPubMed
25.
go back to reference Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O: Serum levels of microRNAs in patients with heart failure. European journal of heart failure. 2012, 14 (2): 147-154. 10.1093/eurjhf/hfr155.CrossRefPubMed Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O: Serum levels of microRNAs in patients with heart failure. European journal of heart failure. 2012, 14 (2): 147-154. 10.1093/eurjhf/hfr155.CrossRefPubMed
26.
go back to reference Whiteley W, Tian Y, Jickling GC: Blood biomarkers in stroke: research and clinical practice. International journal of stroke : official journal of the International Stroke Society. 2012, 7 (5): 435-439. 10.1111/j.1747-4949.2012.00784.x.CrossRef Whiteley W, Tian Y, Jickling GC: Blood biomarkers in stroke: research and clinical practice. International journal of stroke : official journal of the International Stroke Society. 2012, 7 (5): 435-439. 10.1111/j.1747-4949.2012.00784.x.CrossRef
27.
go back to reference Jickling GC, Sharp FR: Blood biomarkers of ischemic stroke. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2011, 8 (3): 349-360. 10.1007/s13311-011-0050-4.CrossRef Jickling GC, Sharp FR: Blood biomarkers of ischemic stroke. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2011, 8 (3): 349-360. 10.1007/s13311-011-0050-4.CrossRef
28.
go back to reference Gan CS, Wang CW, Tan KS: Circulatory microRNA-145 expression is increased in cerebral ischemia. Genetics and molecular research: GMR. 2012, 11 (1): 147-152. 10.4238/2012.January.27.1.CrossRefPubMed Gan CS, Wang CW, Tan KS: Circulatory microRNA-145 expression is increased in cerebral ischemia. Genetics and molecular research: GMR. 2012, 11 (1): 147-152. 10.4238/2012.January.27.1.CrossRefPubMed
29.
go back to reference Mayr M, Zampetaki A, Kiechl S: MicroRNA biomarkers for failing hearts?. European heart journal. 2013, 34 (36): 2782-2783. 10.1093/eurheartj/eht261.CrossRefPubMed Mayr M, Zampetaki A, Kiechl S: MicroRNA biomarkers for failing hearts?. European heart journal. 2013, 34 (36): 2782-2783. 10.1093/eurheartj/eht261.CrossRefPubMed
30.
go back to reference Sun C, Alkhoury K, Wang YI, Foster GA, Radecke CE, Tam K, Edwards CM, Facciotti MT, Armstrong EJ, Knowlton AA, et al: IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal. Circulation research. 2012, 111 (8): 1054-1064. 10.1161/CIRCRESAHA.112.270314.CrossRefPubMed Sun C, Alkhoury K, Wang YI, Foster GA, Radecke CE, Tam K, Edwards CM, Facciotti MT, Armstrong EJ, Knowlton AA, et al: IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal. Circulation research. 2012, 111 (8): 1054-1064. 10.1161/CIRCRESAHA.112.270314.CrossRefPubMed
31.
go back to reference Hulsmans M, Holvoet P: MicroRNA-containing microvesicles regulating inflammation in association with atherosclerotic disease. Cardiovascular research. 2013, 100 (1): 7-18. 10.1093/cvr/cvt161.CrossRefPubMed Hulsmans M, Holvoet P: MicroRNA-containing microvesicles regulating inflammation in association with atherosclerotic disease. Cardiovascular research. 2013, 100 (1): 7-18. 10.1093/cvr/cvt161.CrossRefPubMed
32.
go back to reference Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO: Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature cell biology. 2007, 9 (6): 654-659. 10.1038/ncb1596.CrossRefPubMed Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO: Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature cell biology. 2007, 9 (6): 654-659. 10.1038/ncb1596.CrossRefPubMed
33.
go back to reference Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, et al: Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nature cell biology. 2012, 14 (3): 249-256. 10.1038/ncb2441.CrossRefPubMed Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, et al: Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nature cell biology. 2012, 14 (3): 249-256. 10.1038/ncb2441.CrossRefPubMed
34.
go back to reference Tadokoro H, Umezu T, Ohyashiki K, Hirano T, Ohyashiki JH: Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells. The Journal of biological chemistry. 2013, PMID:24133215 Tadokoro H, Umezu T, Ohyashiki K, Hirano T, Ohyashiki JH: Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells. The Journal of biological chemistry. 2013, PMID:24133215
35.
go back to reference Curka PA, Chisholm CD: High-pressure water injection injury to the hand. The American journal of emergency medicine. 1989, 7 (2): 165-167. 10.1016/0735-6757(89)90130-7.CrossRefPubMed Curka PA, Chisholm CD: High-pressure water injection injury to the hand. The American journal of emergency medicine. 1989, 7 (2): 165-167. 10.1016/0735-6757(89)90130-7.CrossRefPubMed
Metadata
Title
Circulating miR-30a, miR-126 and let-7b as biomarker for ischemic stroke in humans
Authors
Guangwen Long
Feng Wang
Huaping Li
Zhongwei Yin
Chaugai Sandip
Yan Lou
Yan Wang
Chen Chen
Dao Wen Wang
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2013
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/1471-2377-13-178

Other articles of this Issue 1/2013

BMC Neurology 1/2013 Go to the issue