Characterization of circRNA-Associated-ceRNA Networks in a Senescence-Accelerated Mouse Prone 8 Brain

• Published in: Molecular therapy Vol. 25; no. 9; pp. 2053 - 2061
• Main Authors: Zhang, Shuai, Zhu, Dina, Li, Hong, Li, Hejian, Feng, Chengqiang, Zhang, Wensheng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.09.2017; Elsevier Limited; American Society of Gene & Cell Therapy
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Animals; Brain - metabolism; Brain - physiopathology; Brain research; circRNA-associated-ceRNA; Cluster Analysis; Computational Biology - methods; Disease; Disease Models, Animal; Gene Expression Profiling; Gene Expression Regulation; Gene Ontology; Gene Regulatory Networks; Genes; Genetic Association Studies; Genomes; Maze Learning; Memory; Mice; Mice, Transgenic; MicroRNAs - genetics; Myelin; Neurodegenerative diseases; Original; Ribonucleic acid; RNA; RNA - genetics; RNA Interference; RNA, Messenger - genetics; SAMP8; Senescence; Software; China; Alzheimer’s disease; circRNA-associated-ceRNA; SAMP8
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2017.06.009

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases. Although many researchers have attempted to explain the origins of AD, developing an effective strategy in AD clinical therapy is difficult. Recent studies have revealed a potential link between AD and circRNA-associated-ceRNA networks. However, few genome-wide studies have identified the potential circRNA-associated-ceRNA pairs involved in AD. In this study, we systematically explored the circRNA-associated-ceRNA mechanism in a 7-month-old senescence-accelerated mouse prone 8 (SAMP8) model brain through deep RNA sequencing. We obtained 235 significantly dysregulated circRNA transcripts, 30 significantly dysregulated miRNAs, and 1,202 significantly dysregulated mRNAs. We then constructed the most comprehensive circRNA-associated-ceRNA networks in SAMP8 brain. GO analysis revealed that these networks were involved in regulating the development of AD from various angles, for instance, axon terminus (GO: 0043679) and synapse (GO: 0045202). Following rigorous selection, we discovered that the circRNA-associated-ceRNA networks in this AD mouse model were mainly involved in the regulation of Aβ clearance (Hmgb2) and myelin function (Dio2). This research is the first to provide a systematic dissection of circRNA-associated-ceRNA profiling in SAMP8 mouse brain. The selected circRNA-associated-ceRNA networks can profoundly affect the diagnosis and therapy of AD in the future. circRNA inhibits the function of miRNA as miRNA sponges through the ceRNA network. Zhang et al. explored mouse brain genome-wide circRNA-associated-ceRNA networks between 7-month-old SAMP8 and SAMR1 models through deep RNA-seq and listed two ceRNA (circRNA-associated-ceRNA)-related genes (Hmgb2 and Dio2) that were most likely involved in AD.