Su Lining, Li Renqing, Zhang Zhiqing, Liu Jijia, Du Jingkao, Wei Huiping
Department of Basic Medicine, Hebei North University, Zhangjiakou, China.
Ageing Res Rev. 2022 Jan;73:101497. doi: 10.1016/j.arr.2021.101497. Epub 2021 Oct 26.
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by decreased memory and cognitive functions. Exosomes carry a variety of important information such as proteins, lipids, DNA and RNA of mother cells. It is reported that exosomes play critical roles in nervous system physiology and neurodegenerative diseases. However, the functions of exosomes in AD progression are not fully elucidated. In this study, we detected the expression pattern of mRNAs and miRNAs in exosomes derived from the AD and health mice. A total of 1320 mRNAs and 29 miRNAs were differentially expressed in exosomes between the two groups. Subsequently, the downregulation of Chi3l1 and upregulation of Rhog in AD mice were verified by qRT-PCR. Meanwhile, the downregulation of miR-148a-5p and upregulation of miR-27a-5p in AD group were also tested by qRT-PCR. The functions of differentially expressed mRNAs and potential target genes of miRNAs were determined by GO and KEGG analysis. According to the ceRNA hypothesis, we established an integrated ceRNA network of circRNA-lncRNA-miRNA-mRNA. In conclusion, exosomal lncRNAs, mRNAs, circRNAs and miRNAs were identified to participate in the progression of AD which might be possible biomarkers and therapeutic targets for AD.
阿尔茨海默病（AD）是一种以记忆和认知功能减退为特征的进行性神经退行性疾病。外泌体携带母细胞的多种重要信息，如蛋白质、脂质、DNA和RNA。据报道，外泌体在神经系统生理学和神经退行性疾病中起关键作用。然而，外泌体在AD进展中的功能尚未完全阐明。在本研究中，我们检测了来自AD小鼠和健康小鼠的外泌体中mRNA和miRNA的表达模式。两组外泌体中共有1320种mRNA和29种miRNA差异表达。随后，通过qRT-PCR验证了AD小鼠中Chi3l1的下调和Rhog的上调。同时，也通过qRT-PCR检测了AD组中miR-148a-5p的下调和miR-27a-5p的上调。通过GO和KEGG分析确定差异表达mRNA和miRNA潜在靶基因的功能。根据ceRNA假说，我们建立了circRNA-lncRNA-miRNA-mRNA的综合ceRNA网络。总之，已确定外泌体lncRNA、mRNA、circRNA和miRNA参与AD的进展，它们可能是AD的生物标志物和治疗靶点。
