Research Paper Volume 12, Issue 3 pp 2897—2920
Identifying lncRNA–miRNA–mRNA networks to investigate Alzheimer’s disease pathogenesis and therapy strategy
- 1 Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen 518000, Guangdong Province, China
- 2 Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen 518000, Guangdong Province, China
- 3 Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen 518000, Guangdong Province, China
- 4 Division of Life Science, The Hong Kong University of Science and Technology, Kowloon, Hong Kong 999077, China
Received: September 27, 2019 Accepted: January 19, 2020 Published: February 7, 2020
https://doi.org/10.18632/aging.102785How to Cite
Abstract
Alzheimer’s disease (AD), the most common cause of dementia, leads to neuronal damage and deterioration of cognitive functions in aging brains. There is evidence suggesting the participation of noncoding RNAs in AD-associated pathophysiology. A potential linkage between AD and lncRNA-associated competing endogenous RNA (ceRNA) networks has been revealed. Nevertheless, there are still no genome-wide studies which have identified the lncRNA-associated ceRNA pairs involved in AD. For this reason, deep RNA-sequencing was performed to systematically investigate lncRNA-associated ceRNA mechanisms in AD model mice (APP/PS1) brains. Our results identified 487, 89, and 3,025 significantly dysregulated lncRNAs, miRNAs, and mRNAs, respectively, and the most comprehensive lncRNA-associated ceRNA networks to date are constructed in the APP/PS1 brain. GO analysis revealed the involvement of the identified networks in regulating AD development from distinct origins, such as synapses and dendrites. Following rigorous selection, the lncRNA-associated ceRNA networks in this AD mouse model were found to be mainly involved in synaptic plasticity as well as memory (Akap5) and regulation of amyloid-β (Aβ)-induced neuroinflammation (Klf4). This study presents the first systematic dissection of lncRNA-associated ceRNA profiles in the APP/PS1 mouse brain. The identified lncRNA-associated ceRNA networks could provide insights that facilitate AD diagnosis and future treatment strategies.