Identification of a hippocampal IncRNA-regulating network in cognitive dysfunction caused by chronic cerebral hypoperfusion

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 IncRNA is involved in cognitive dysfunction caused by CCH has not yet been reported. In the present study, we identified the altered IncRNAs and mRNAs by deep RNA sequencing. A total of 128 mRNAs and 91 IncRNAs were up-regulated, and 108 mRNAs and 98 IncRNAs were down-regulated. Real-time reverse transcription-polymerase chain reaction verified the reliability of the IncRNA 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 IncRNAs were correlated with DE mRNAs. By predicting the miRNA in which both DE IncRNAs and DE mRNAs bind together, we constructed a competitive endogenous RNA network. In this IncRNAs-miRNAs-mRNAs network, 559 IncRNA-miRNA-mRNA targeted pairs were identified, including 83 IncRNAs, 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.