Title:Whole Transcriptome Sequencing of Peripheral Blood Identifies the
Alzheimer's Disease-Related circRNA-miRNA-lncRNA Pathway
Volume: 21
Issue: 2
Author(s): Yucheng Gu, Nihong Chen, Lin Zhu, Xiangliang Chen, Teng Jiang and Yingdong Zhang*
Affiliation:
- Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
Keywords:
Alzheimer’s dementia, Alzheimer’s disease continuum, clinical dementia rating, mild cognitive impairment, whole transcriptome sequencing, circRNA-miRNA-lncRNA.
Abstract:
Background: Previous studies on transcriptional profiles suggested dysregulation of
multiple RNA species in Alzheimer’s disease. However, despite recent investigations revealing
various aspects of circular RNA (circRNA)-associated competing endogenous RNA (ceRNA)
networks in Alzheimer's Disease (AD) pathogenesis, few genome-wide studies have explored
circRNA-associated profiles in AD patients exhibiting varying degrees of cognitive loss.
Objective: To investigate the potential pathogenesis-related molecular biological changes in the
various stages of AD progression.
Methods: Whole transcriptome sequencing was performed on the peripheral blood of 7 normal
cognition (NC) subjects, 8 patients with mild cognitive impairment, 8 AD patients with mild
dementia (miD), and 7 AD patients with moderate dementia (moD). Gene Ontology (GO) analysis
and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted
to predict the potential functions of the maternal genes of microRNAs (miRNAs), circRNAs and
long non-coding RNAs (lncRNAs). The construction of ceRNA network was performed between
the NC group and each diseased group based on the differently expressed RNAs.
Results: In total, 3568 messenger RNAs (mRNAs), 142 miRNAs, 990 lncRNAs, and 183
circRNAs were identified as significantly differentially expressed across the four groups. GO
and KEGG enrichment analysis revealed the significant roles of GTPase activity and the MAPK
signaling pathway in AD pathogenesis. A circRNA-miRNA-lncRNA ceRNA pathway, characterized
by the downregulated hsa-miR-7-5p and upregulated hsa_circ_0001170, was identified
based on the differentially expressed RNAs between the NC group and the moD group.
Conclusion: The study suggests that circRNAs may be independent of mRNAs in AD pathogenesis
and holds promise as potential biomarkers for AD clinical manifestations and pathological
changes.
