Open AccessPossible epigenetic regulatory effect of dysregulated circular RNAs in Alzheimer’s disease model
Author(s) -
Woojin Lee,
Jangsup Moon,
Daejong Jeon,
Yeong-Gil Shin,
Jung Suk Yoo,
Dong Kyu Park,
Sang Kun Lee,
Keun Hwa Jung,
KyungIl Park,
Ki Young Jung,
Manho Kim,
Sang Kun Lee,
Kon Chu
Publication year - 2019
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-019-48471-z
Subject(s) - microrna , circular rna , biology , epigenetics , microarray analysis techniques , microarray , regulation of gene expression , computational biology , disease , pathogenesis , messenger rna , gene expression , non coding rna , gene regulatory network , gene , bioinformatics , genetics , medicine , immunology , pathology
As circular RNAs (circRNAs) regulates the effect of micro RNAs (miRNAs), circRNA–miRNA-mRNA network might be implicated in various disease pathogenesis. Therefore, we evaluated the dysregulated circRNAs in the Tg2576 mouse Alzheimer’s disease (AD) model, their possible regulatory effects on downstream target mRNAs, and their pathomechanistic role during the disease progression. The microarray-based circRNA expression analysis at seven- and twelve-months of ages (7 M and 12 M) returned 101 dysregulated circRNAs at 7 M (55 up-regulated and 46 down-regulated) and twelve dysregulated circRNAs at 12 M (five up-regulated and seven down-regulated). For each dysregulated circRNA, potential target miRNAs and their downstream target mRNAs were searched. Dysregulation of circRNAs was associated with increased frequency of relevant dysregulation of their downstream target mRNAs. Those differentially expressed circRNA–miRNA-mRNA regulatory network included 2,275 networks (876 for up-regulated circRNAs and 1,399 for down-regulated circRNAs) at 7 M and 38 networks (25 for up-regulated circRNAs and 13 for down-regulated circRNAs) at 12 M. Gene ontology (GO) and pathway analyses demonstrated that the dysregulated mRNAs in those networks represent the AD pathomechanism at each disease stage. We concluded that the dysregulated circRNAs might involve in the AD pathogenesis by modulating disease relevant mRNAs via circRNA–miRNA-mRNA regulatory networks.