Analysis of LncRNA and mRNA expression profiles and regulatory network in the brain tissue of a mouse model with Alzheimer's disease
Li Jinping1, Li Xiaoxiong1, Ma Linqiu1, Ma Jingjing1, Hong Wenjuan1, Huang Jie1, Hou Mingliang1, Zhou Huadong1,2
1Department of Neurology, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; 2Department of Neurology, Army Medical Center of PLA, Chongqing 400020, China
Abstract：Objective This study aims to investigate the expression profiles of long non-coding RNA(LncRNA) and messenger RNA (mRNA) in the brain tissue of a mouse model with Alzheimer's disease (AD), construct a regulatory network of competing endogenous RNA(ceRNA), and analyze the potential role of differentially expressed LncRNA in the pathogenesis of AD. Methods Three 10-month-old male APP/PS1 transgenic mice were selected as AD group, and three ordinary C57 mice matched for age and body weight were selected as control group. The expression levels of LncRNA and mRNA in the brain tissues of the two groups were detected by gene chip technology, and differentially expressed LncRNA and mRNA were screened. Real-time quantitative polymerase chain reaction (qRT-PCR) was performed on differentially expressed LncRNAs to verify the reliability of the gene chip results. Differentially expressed mRNAs were evaluated by Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses. Six differentially expressed LncRNAs were selected to construct the ceRNA network and predict the function of target genes. Results Compared with the control group, 933 LncRNAs were differentially expressed by more than 1.5 times in the AD group, 222 of which were up-regulated and 711 were down-regulated. A total of 529 mRNAs were differentially expressed by more than 1.5 times, of which 189 were up-regulated and 340 were down-regulated. The results of qRT-PCR showed that the up-or down-regulation trend of 7 differentially expressed LncRNAs was consistent with the gene chip results, and the differences were statistically significant (all P values <0.05). The GO and KEGG pathway analysis showed that the differentially expressed genes were mainly involved in amino acid metabolism, inflammation response, and immune response. Functional enrichment analysis of the ceRNA regulatory network target genes showed that LncRNA was significantly enriched in insulin resistance and AGE-RAGE signaling pathways in diabetic complications. Conclusion The expression profiles of LncRNAs in the brain tissue of APP/PS1 mice significantly changed. The ceRNA regulatory network constructed by LncRNA Dgkb and Svip can enhance research on the molecular mechanism of AD pathogenesis, and differentially expressed LncRNAs or pathways may become potential therapeutic targets.
李金平, 李小雄, 马琳秋, 马晶晶, 洪文娟, 黄洁, 侯明亮, 周华东. 阿尔茨海默病小鼠脑组织长链非编码RNA与信使RNA表达谱及调控网络的分析[J]. 中华解剖与临床杂志, 2023, 28(2): 112-120.
Li Jinping, Li Xiaoxiong, Ma Linqiu, Ma Jingjing, Hong Wenjuan, Huang Jie, Hou Mingliang, Zhou Huadong. Analysis of LncRNA and mRNA expression profiles and regulatory network in the brain tissue of a mouse model with Alzheimer's disease. Chinese Journal of Anatomy and Clinics, 2023, 28(2): 112-120.
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