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Published in: Neurological Sciences 1/2015

01-01-2015 | Original Article

miRNA functional synergistic network analysis of mice with ischemic stroke

Authors: Shuping Xiao, Yingwen Ma, Haiying Zhu, Hongyu Sun, Yanling Yin, Guangkun Feng

Published in: Neurological Sciences | Issue 1/2015

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Abstract

This study aimed to identify potential miRNAs highly associated with the response to brain ischemic stroke. The miRNAs microarray expression profiles data were downloaded from Gene Expression Omnibus database under accession number GSE51586, including three ischemia and three ipsilateral normal samples from mouse brain tissues. Limma package was used to identify differentially expressed miRNAs between ischemia and ipsilateral normal samples. The common target genes of miRNA predicted from TargetScan, PicTar, miRanda and DIANA-microT databases were used as the candidate subset in which functional modules were identified by performing gene ontology enrichment analysis using ClusterProfile. Finally, the miRNA functional synergistic network was constructed by assembling all miRNA synergistic pairs. Fifty-one differentially expressed miRNAs were identified between ischemia and ipsilateral normal samples, including 32 up- and 19 down-regulated miRNAs. Among them, 24 miRNAs can commonly regulate at least one target gene and thus were used to construct a network, which included 274 pairs of co-regulating miRNAs. Further, 242 pairs of miRNAs interaction involving 23 miRNAs were shown to be synergetic in function. Sixteen miRNAs forming 20 miRNAs interaction pairs participated in inflammatory response, such as mir-185 and mir-674-3p. The 16 miRNAs related to inflammatory response during ischemic stroke may provide underlying targets for prevention and treatment of stroke.
Literature
1.
go back to reference Panella M, Brambilla R, Marchisio S, Di Stanislao F (2008) Reducing stroke in-hospital mortality: organized care is a complex intervention. Stroke 39:e186–e186CrossRefPubMed Panella M, Brambilla R, Marchisio S, Di Stanislao F (2008) Reducing stroke in-hospital mortality: organized care is a complex intervention. Stroke 39:e186–e186CrossRefPubMed
2.
go back to reference Seshadri S, Beiser A, Kelly-Hayes M, Kase CS, Au R, Kannel WB, Wolf PA (2006) The lifetime risk of stroke estimates from the Framingham Study. Stroke 37:345–350CrossRefPubMed Seshadri S, Beiser A, Kelly-Hayes M, Kase CS, Au R, Kannel WB, Wolf PA (2006) The lifetime risk of stroke estimates from the Framingham Study. Stroke 37:345–350CrossRefPubMed
3.
go back to reference Rosamond W, Flegal K, Furie K et al (2008) American heart association statistics committee and stroke statistics subcommittee. Heart disease and stroke statistics—2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 117:e25–e146CrossRefPubMed Rosamond W, Flegal K, Furie K et al (2008) American heart association statistics committee and stroke statistics subcommittee. Heart disease and stroke statistics—2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 117:e25–e146CrossRefPubMed
4.
go back to reference Mattson M, Duan W, Pedersen W, Culmsee C (2001) Neurodegenerative disorders and ischemic brain diseases. Apoptosis 6:69–81CrossRefPubMed Mattson M, Duan W, Pedersen W, Culmsee C (2001) Neurodegenerative disorders and ischemic brain diseases. Apoptosis 6:69–81CrossRefPubMed
5.
go back to reference Richard Green A, Odergren T, Ashwood T (2003) Animal models of stroke: do they have value for discovering neuroprotective agents? Trends Pharmacol Sci 24:402–408CrossRefPubMed Richard Green A, Odergren T, Ashwood T (2003) Animal models of stroke: do they have value for discovering neuroprotective agents? Trends Pharmacol Sci 24:402–408CrossRefPubMed
6.
go back to reference O’collins VE, Macleod MR, Donnan GA, Horky LL, Van Der Worp BH, Howells DW (2006) 1,026 experimental treatments in acute stroke. Ann Neurol 59:467–477CrossRefPubMed O’collins VE, Macleod MR, Donnan GA, Horky LL, Van Der Worp BH, Howells DW (2006) 1,026 experimental treatments in acute stroke. Ann Neurol 59:467–477CrossRefPubMed
7.
go back to reference Lo EH, Dalkara T, Moskowitz MA (2003) Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 4:399–414CrossRefPubMed Lo EH, Dalkara T, Moskowitz MA (2003) Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 4:399–414CrossRefPubMed
8.
go back to reference Hossmann K-A (2006) Pathophysiology and therapy of experimental stroke. Cell Mol Neurobiol 26:1055–1081CrossRef Hossmann K-A (2006) Pathophysiology and therapy of experimental stroke. Cell Mol Neurobiol 26:1055–1081CrossRef
9.
go back to reference Liesz A, Suri-Payer E, Veltkamp C et al (2009) Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat Med 15:192–199CrossRefPubMed Liesz A, Suri-Payer E, Veltkamp C et al (2009) Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat Med 15:192–199CrossRefPubMed
11.
go back to reference Dirnagl U, Klehmet J, Braun JS et al (2007) Stroke-induced immunodepression experimental evidence and clinical relevance. Stroke 38:770–773CrossRefPubMed Dirnagl U, Klehmet J, Braun JS et al (2007) Stroke-induced immunodepression experimental evidence and clinical relevance. Stroke 38:770–773CrossRefPubMed
12.
13.
go back to reference Whitaker JN (2001) The potential for harm or benefit from inflammatory processes in stroke. Arch Neurol 58:674PubMed Whitaker JN (2001) The potential for harm or benefit from inflammatory processes in stroke. Arch Neurol 58:674PubMed
15.
go back to reference Yuan X, Liu C, Yang P, He S, Liao Q, Kang S, Zhao Y (2009) Clustered microRNAs’ coordination in regulating protein–protein interaction network. BMC Syst Biol 3:65PubMedCentralCrossRefPubMed Yuan X, Liu C, Yang P, He S, Liao Q, Kang S, Zhao Y (2009) Clustered microRNAs’ coordination in regulating protein–protein interaction network. BMC Syst Biol 3:65PubMedCentralCrossRefPubMed
16.
go back to reference Dhiraj DK, Chrysanthou E, Mallucci GR, Bushell M (2013) miRNAs-19b,-29b-2* and-339-5p show an early and sustained up-regulation in ischemic models of stroke. PLoS One 8:e83717PubMedCentralCrossRefPubMed Dhiraj DK, Chrysanthou E, Mallucci GR, Bushell M (2013) miRNAs-19b,-29b-2* and-339-5p show an early and sustained up-regulation in ischemic models of stroke. PLoS One 8:e83717PubMedCentralCrossRefPubMed
17.
go back to reference Diboun I, Wernisch L, Orengo CA, Koltzenburg M (2006) Microarray analysis after RNA amplification can detect pronounced differences in gene expression using limma. BMC Genom 7:252CrossRef Diboun I, Wernisch L, Orengo CA, Koltzenburg M (2006) Microarray analysis after RNA amplification can detect pronounced differences in gene expression using limma. BMC Genom 7:252CrossRef
18.
go back to reference Maragkakis M, Vergoulis T, Alexiou P et al (2011) DIANA-microT web server upgrade supports fly and worm miRNA target prediction and bibliographic miRNA to disease association. Nucleic Acids Res 39:W145–W148PubMedCentralCrossRefPubMed Maragkakis M, Vergoulis T, Alexiou P et al (2011) DIANA-microT web server upgrade supports fly and worm miRNA target prediction and bibliographic miRNA to disease association. Nucleic Acids Res 39:W145–W148PubMedCentralCrossRefPubMed
19.
go back to reference Shannon P, Markiel A, Ozier O et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504PubMedCentralCrossRefPubMed Shannon P, Markiel A, Ozier O et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504PubMedCentralCrossRefPubMed
20.
go back to reference Muir KW, Tyrrell P, Sattar N, Warburton E (2007) Inflammation and ischaemic stroke. Curr Opin Neurol 20:334–342CrossRefPubMed Muir KW, Tyrrell P, Sattar N, Warburton E (2007) Inflammation and ischaemic stroke. Curr Opin Neurol 20:334–342CrossRefPubMed
21.
go back to reference Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391–397CrossRefPubMed Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391–397CrossRefPubMed
22.
go back to reference Pun PB, Lu J, Moochhala S (2009) Involvement of ROS in BBB dysfunction. Free Radic Res 43:348–364CrossRefPubMed Pun PB, Lu J, Moochhala S (2009) Involvement of ROS in BBB dysfunction. Free Radic Res 43:348–364CrossRefPubMed
23.
go back to reference Che X, Ye W, Panga L, Wu D-C, Yang G-Y (2001) Monocyte chemoattractant protein-1 expressed in neurons and astrocytes during focal ischemia in mice. Brain Res 902:171–177CrossRefPubMed Che X, Ye W, Panga L, Wu D-C, Yang G-Y (2001) Monocyte chemoattractant protein-1 expressed in neurons and astrocytes during focal ischemia in mice. Brain Res 902:171–177CrossRefPubMed
24.
go back to reference Chen C-Z, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86CrossRefPubMed Chen C-Z, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86CrossRefPubMed
25.
go back to reference Cobb BS, Nesterova TB, Thompson E et al (2005) T cell lineage choice and differentiation in the absence of the RNase III enzyme dicer. J Exp Med 201:1367–1373PubMedCentralCrossRefPubMed Cobb BS, Nesterova TB, Thompson E et al (2005) T cell lineage choice and differentiation in the absence of the RNase III enzyme dicer. J Exp Med 201:1367–1373PubMedCentralCrossRefPubMed
27.
go back to reference Muljo SA, Ansel KM, Kanellopoulou C, Livingston DM, Rao A, Rajewsky K (2005) Aberrant T cell differentiation in the absence of dicer. J Exp Med 202:261–269PubMedCentralCrossRefPubMed Muljo SA, Ansel KM, Kanellopoulou C, Livingston DM, Rao A, Rajewsky K (2005) Aberrant T cell differentiation in the absence of dicer. J Exp Med 202:261–269PubMedCentralCrossRefPubMed
28.
go back to reference Li Q-J, Chau J, Ebert PJ et al (2007) miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 129:147–161CrossRefPubMed Li Q-J, Chau J, Ebert PJ et al (2007) miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 129:147–161CrossRefPubMed
29.
go back to reference O’connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D (2007) MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA 104:1604–1609PubMedCentralCrossRefPubMed O’connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D (2007) MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA 104:1604–1609PubMedCentralCrossRefPubMed
30.
go back to reference Bhaumik D, Scott G, Schokrpur S, Patil C, Campisi J, Benz C (2008) Expression of microRNA-146 suppresses NF-κB activity with reduction of metastatic potential in breast cancer cells. Oncogene 27:5643–5647PubMedCentralCrossRefPubMed Bhaumik D, Scott G, Schokrpur S, Patil C, Campisi J, Benz C (2008) Expression of microRNA-146 suppresses NF-κB activity with reduction of metastatic potential in breast cancer cells. Oncogene 27:5643–5647PubMedCentralCrossRefPubMed
31.
go back to reference Perry MM, Williams AE, Tsitsiou E, Larner-Svensson HM, Lindsay MA (2009) Divergent intracellular pathways regulate interleukin-1β-induced miR-146a and miR-146b expression and chemokine release in human alveolar epithelial cells. FEBS Lett 583:3349–3355CrossRefPubMed Perry MM, Williams AE, Tsitsiou E, Larner-Svensson HM, Lindsay MA (2009) Divergent intracellular pathways regulate interleukin-1β-induced miR-146a and miR-146b expression and chemokine release in human alveolar epithelial cells. FEBS Lett 583:3349–3355CrossRefPubMed
32.
go back to reference Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, David M (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449:919–922PubMedCentralCrossRefPubMed Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, David M (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449:919–922PubMedCentralCrossRefPubMed
33.
go back to reference Otsuka M, Jing Q, Georgel P et al (2007) Hypersusceptibility to vesicular stomatitis virus infection in dicer1-deficient mice is due to impaired miR24 and miR93 expression. Immunity 27:123–134CrossRefPubMed Otsuka M, Jing Q, Georgel P et al (2007) Hypersusceptibility to vesicular stomatitis virus infection in dicer1-deficient mice is due to impaired miR24 and miR93 expression. Immunity 27:123–134CrossRefPubMed
34.
go back to reference Jeyaseelan K, Lim KY, Armugam A (2008) MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke 39:959–966CrossRefPubMed Jeyaseelan K, Lim KY, Armugam A (2008) MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke 39:959–966CrossRefPubMed
35.
go back to reference Liu D-Z, Tian Y, Ander BP et al (2009) Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures. J Cereb Blood Flow Metab 30:92–101PubMedCentralCrossRefPubMed Liu D-Z, Tian Y, Ander BP et al (2009) Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures. J Cereb Blood Flow Metab 30:92–101PubMedCentralCrossRefPubMed
36.
go back to reference Hulsmans M, De Keyzer D, Holvoet P (2011) MicroRNAs regulating oxidative stress and inflammation in relation to obesity and atherosclerosis. FASEB J 25:2515–2527CrossRefPubMed Hulsmans M, De Keyzer D, Holvoet P (2011) MicroRNAs regulating oxidative stress and inflammation in relation to obesity and atherosclerosis. FASEB J 25:2515–2527CrossRefPubMed
37.
go back to reference Yang X, Li Z, Su Z, Davis K, Chen T, Mendrick D, Salminen W (2011) Urinary microRNAs as noninvasive biomarkers for acetaminophen-induced liver injury. J Postgenom Drug Biomark Develop 1(2153–0769):1000101 Yang X, Li Z, Su Z, Davis K, Chen T, Mendrick D, Salminen W (2011) Urinary microRNAs as noninvasive biomarkers for acetaminophen-induced liver injury. J Postgenom Drug Biomark Develop 1(2153–0769):1000101
Metadata
Title
miRNA functional synergistic network analysis of mice with ischemic stroke
Authors
Shuping Xiao
Yingwen Ma
Haiying Zhu
Hongyu Sun
Yanling Yin
Guangkun Feng
Publication date
01-01-2015
Publisher
Springer Milan
Published in
Neurological Sciences / Issue 1/2015
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-014-1904-4

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