Research Paper Volume 12, Issue 19 pp 19520—19538
Identification of a hippocampal lncRNA-regulating network in cognitive dysfunction caused by chronic cerebral hypoperfusion
- 1 Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, China
- 2 Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
- 3 Department of Neurology, Central Hospital of Zhengzhou, Zhengzhou, China
- 4 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- 5 Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, China
Received: April 10, 2020 Accepted: July 23, 2020 Published: October 11, 2020
https://doi.org/10.18632/aging.103901How to Cite
Copyright: © 2020 Yao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Cognitive dysfunction caused by chronic cerebral hypoperfusion is a common underlying cause of many cognition-related neurodegenerative diseases. The mechanisms of cognitive dysfunction caused by CCH are not clear. Long non-coding RNA is involved in synaptic plasticity and cognitive function, but whether lncRNA is involved in cognitive dysfunction caused by CCH has not yet been reported. In the present study, we identified the altered lncRNAs and mRNAs by deep RNA sequencing. A total of 128 mRNAs and 91 lncRNAs were up-regulated, and 108 mRNAs and 98 lncRNAs were down-regulated. Real-time reverse transcription-polymerase chain reaction verified the reliability of the lncRNA and mRNA sequencing. Gene Ontology and KEGG pathway analyses showed that differentially-expressed mRNAs were related to peptide antigen binding, the extracellular space, the monocarboxylic acid transport, and tryptophan metabolism. The co-expression analysis showed that 161 differentially expressed lncRNAs were correlated with DE mRNAs. By predicting the miRNA in which both DE lncRNAs and DE mRNAs bind together, we constructed a competitive endogenous RNA network. In this lncRNAs-miRNAs-mRNAs network, 559 lncRNA-miRNA-mRNA targeted pairs were identified, including 83 lncRNAs, 67 miRNAs, and 108 mRNAs. Through GO and KEGG pathway analysis, we further analyzed and predicted the regulatory function and potential mechanism of ceRNA network regulation. Our results are helpful for understanding the pathogenesis of cognitive dysfunction caused by CCH and provide direction for further research.
Abbreviations
CAMs: cell adhesion molecules; CCH: chronic cerebral hypoperfusion; ceRNA: competitive endogenous RNA; ChAT: choline O-acetyltransferase; COR: correlation coefficient; DAT: dopamine transporter; DE lncRNAs: differentially expressed lncRNAs; DE mRNAs: differentially-expressed mRNAs; FPKM: fragments per kilobase per million; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; lncRNA: long non-coding RNA; (qRT-PCR); ncRNAs: non-coding RNAs; NSFC: National Natural Science Foundation of China; SEM: standard error of the mean.