Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jan 8:2018:8354350.
doi: 10.1155/2018/8354350. eCollection 2018.

Systematic Analysis of RNA Regulatory Network in Rat Brain after Ischemic Stroke

Juan Liu  1 , Kun-Shan Zhang  2 , Bin Hu  3 , Si-Guang Li  2 , Qing Li  3 , Yu-Ping Luo  2 , Yang Wang  3 , Zhi-Feng Deng  1
Affiliations

Systematic Analysis of RNA Regulatory Network in Rat Brain after Ischemic Stroke

Juan Liu et al. Biomed Res Int. .

Abstract

Although extensive studies have identified large number of microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in ischemic stroke, the RNA regulation network response to focal ischemia remains poorly understood. In this study, we simultaneously interrogate the expression profiles of lncRNAs, miRNAs, and mRNAs changes during focal ischemia induced by transient middle cerebral artery occlusion. A set of 1924 novel lncRNAs were identified and may involve brain injury and DNA repair as revealed by coexpression network analysis. Furthermore, many short interspersed elements (SINE) mediated lncRNA:mRNA duplexes were identified, implying that lncRNAs mediate Staufen1-mediated mRNA decay (SMD) which may play a role during focal ischemia. Moreover, based on the competitive endogenous RNA (ceRNA) hypothesis, a stroke regulatory ceRNA network which reveals functional lncRNA:miRNA:mRNA interactions was revealed in ischemic stroke. In brief, this work reports a large number of novel lncRNAs responding to focal ischemia and constructs a systematic RNA regulation network which highlighted the role of ncRNAs in ischemic stroke.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Identification of long noncoding RNAs (lncRNAs) in rat brains. (a) A diagram illustrating MCAO model in rat. Whole brain tissue and TTC stains show infarction in the MCA cortex. Area with dashed line shows the tissue region sampled for RNA sequence and real-time PCR analysis. (b) The pipeline of lncRNAs identification in rat brains.
Figure 2
Figure 2
Aberrant expression of lncRNAs in rat brains after ischemic stroke. (a) Heatmap generated from the hierarchical cluster analysis shows the differential expressed genes (lncRNAs, miRNAs, and mRNAs) between ischemia and nonischemia rat brains. Green indicates downregulation and red indicates upregulation. (b) Real-time PCR validation of differential expressed lncRNAs in the ischemia and nonischemia rat brains. (c) Electrophoresis of 10 novel lncRNAs in the ischemia and nonischemia rat brains. (d) KEGG pathway analysis of differential expressed genes in the ischemia and nonischemia rat brains. (e) GO analysis of differential expressed genes in the ischemia and nonischemia rat brains.
Figure 3
Figure 3
lncRNAs mediate SMD in ischemic stroke. (a) Expression of Staufen1 and Staufen2 in the ischemia and nonischemia rat brain after ischemic stroke. (b) Distribution of SINEs (B1, B2, and B4 element) in mRNA 3′UTR and lncRNAs in the ischemia rat brains. (c) Distribution of SINEs in mRNA 3′UTR and lncRNAs in the nonischemia rat brains. (d) SMD regulatory network of differentially expressed genes. (e) SMD network filtered by duplex energy. (f) Examples of two Alu-based lncRNA:mRNA duplex. Red triangle represents lncRNAs and blue square represents coding genes.
Figure 4
Figure 4
ceRNA network in ischemic stroke. (a) miRNAs detected in the rat brains after ischemic stroke. (b) Expression of top 14 miRNAs in the rat brains after ischemic stroke. (c) mRNA-miRNA-lncRNA interactions network in the ischemic stroke. Triangle represents lncRNAs, square represents coding genes, and circles represent miRNAs. Red lines indicate interaction from miRNA to mRNAs and green lines indicate interaction from miRNA to lncRNAs.
See this image and copyright information in PMC

References

    1. Mozaffarian D., Benjamin E. J., Go A. S., et al. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38–e360. doi: 10.1161/CIR.0000000000000350. - DOI - PubMed
    1. Mitsios N., Gaffney J., Kumar P., Krupinski J., Kumar S., Slevin M. Pathophysiology of acute ischaemic stroke: An analysis of common signalling mechanisms and identification of new molecular targets. Pathobiology. 2006;73(4):159–175. doi: 10.1159/000096017. - DOI - PubMed
    1. Deb P., Sharma S., Hassan K. M. Pathophysiologic mechanisms of acute ischemic stroke: an overview with emphasis on therapeutic significance beyond thrombolysis. Pathophysiology. 2010;17(3):197–218. doi: 10.1016/j.pathophys.2009.12.001. - DOI - PubMed
    1. Dharap A., Bowen K., Place R., Li L.-C., Vemuganti R. Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome. Journal of Cerebral Blood Flow & Metabolism. 2009;29(4):675–687. doi: 10.1038/jcbfm.2008.157. - DOI - PMC - PubMed
    1. Jeyaseelan K., Lim K. Y., 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. doi: 10.1161/STROKEAHA.107.500736. - DOI - PubMed