Aberrant Expression Profiles of lncRNAs and Their Associated Nearby Coding Genes in the Hippocampus of the SAMP8 Mouse Model with AD

Honghai Hong; Yousheng Mo; Dongli Li; Zhiheng Xu; Yanfang Liao; Ping Yin; Xinning Liu; Yong Xia; Jiansong Fang; Qi Wang; Shuhuan Fang

doi:10.1016/j.omtn.2020.02.008

Aberrant Expression Profiles of lncRNAs and Their Associated Nearby Coding Genes in the Hippocampus of the SAMP8 Mouse Model with AD

Mol Ther Nucleic Acids. 2020 Jun 5:20:140-154. doi: 10.1016/j.omtn.2020.02.008. Epub 2020 Feb 19.

Authors

Honghai Hong¹, Yousheng Mo², Dongli Li², Zhiheng Xu³, Yanfang Liao², Ping Yin⁴, Xinning Liu², Yong Xia⁴, Jiansong Fang⁵, Qi Wang⁶, Shuhuan Fang⁷

Affiliations

¹ Department of Clinical Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Guangzhou, Guangdong Province, China; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
² Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China.
³ Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China.
⁴ Department of Clinical Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Guangzhou, Guangdong Province, China.
⁵ Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China; DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China. Electronic address: fangjs@gzucm.edu.cn.
⁶ Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China; DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China. Electronic address: 1055898390@qq.com.
⁷ Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China; DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China; Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: fangshuhuan@gzucm.edu.cn.

Abstract

The senescence-accelerated mouse prone 8 (SAMP8) mouse model is a useful model for investigating the fundamental mechanisms involved in the age-related learning and memory deficits of Alzheimer's disease (AD), while the SAM/resistant 1 (SAMR1) mouse model shows normal features. Recent evidence has shown that long non-coding RNAs (lncRNAs) may play an important role in AD pathogenesis. However, a comprehensive and systematic understanding of the function of AD-related lncRNAs and their associated nearby coding genes in AD is still lacking. In this study, we collected the hippocampus, the main area of AD pathological processes, of SAMP8 and SAMR1 animals and performed microarray analysis to identify aberrantly expressed lncRNAs and their associated nearby coding genes, which may contribute to AD pathogenesis. We identified 3,112 differentially expressed lncRNAs and 3,191 differentially expressed mRNAs in SAMP8 mice compared to SAMR1 mice. More than 70% of the deregulated lncRNAs were intergenic and exon sense-overlapping lncRNAs. Gene Ontology (GO) and pathway analyses of the AD-related transcripts were also performed and are described in detail, which imply that metabolic process reprograming was likely related to AD. Furthermore, six lncRNAs and six mRNAs were selected for further validation of the microarray results using quantitative PCR, and the results were consistent with the findings from the microarray. Moreover, we analyzed 780 lincRNAs (also called long "intergenic" non-coding RNAs) and their associated nearby coding genes. Among these lincRNAs, AK158400 had the most genes nearby (n = 13), all of which belonged to the histone cluster 1 family, suggesting regulation of the nucleosome structure of the chromosomal fiber by affecting nearby genes during AD progression. In addition, we also identified 97 aberrant antisense lncRNAs and their associated coding genes. It is likely that these dysregulated lncRNAs and their associated nearby coding genes play a role in the development and/or progression of AD.

Keywords: Alzheimer’s disease; lncRNA-associated nearby genes; lncRNAs.