Huaying Cai, Xing Jin, Luya Jin, Linhui Ni, Di Sun, Xianjun Ding
Department of Neurology, Neuroscience Center, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.
Department of Orthopedic Surgery, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.
Front Aging Neurosci. 2021 Jan 28;12:598606. doi: 10.3389/fnagi.2020.598606. eCollection 2020.
Long non-coding RNAs (lncRNAs) play important roles in the pathogenesis of Alzheimer's disease (AD). However, the functions and regulatory mechanisms of lncRNA are largely unclear. Herein, we obtained 3,158 lncRNAs by microarray re-annotation. A global network of competing endogenous RNAs (ceRNAs) was developed for AD and normal samples were based on the gene expressions profiles. A total of 255 AD-deficient messenger RNA (mRNA)-lncRNAs were identified by the expression correlation analysis. Genes in the dysregulated ceRNAs were found to be mainly enriched in transcription factors and micro RNAs (miRNAs). Analysis of the disordered miRNA in the lncRNA-mRNA network revealed that 40 pairs of lncRNA shared more than one disordered miRNA. Among them, nine lncRNAs were closely associated with AD, Parkinson's disease, and other neurodegenerative diseases. Of note, five lncRNAs were found to be potential biomarkers for AD. Real-time quantitative reverse transcription PCR (qRT-PCR) assay revealed that PART1 was downregulated, while SNHG14 was upregulated in AD serum samples when compared to normal samples. This study elucidates the role of lncRNAs in the pathogenesis of AD and presents new lncRNAs that can be exploited to design diagnostic and therapeutic agents for AD.
长链非编码RNA(lncRNAs)在阿尔茨海默病(AD)的发病机制中发挥着重要作用。然而,lncRNA的功能和调控机制在很大程度上尚不清楚。在此,我们通过微阵列重新注释获得了3158个lncRNAs。基于基因表达谱,构建了AD和正常样本的竞争性内源RNA(ceRNAs)全局网络。通过表达相关性分析共鉴定出255个AD缺陷信使RNA(mRNA)-lncRNAs。发现失调的ceRNAs中的基因主要富集于转录因子和微小RNA(miRNAs)。对lncRNA-mRNA网络中失调的miRNA分析表明,40对lncRNA共享一种以上失调的miRNA。其中,9个lncRNAs与AD、帕金森病和其他神经退行性疾病密切相关。值得注意的是,发现5个lncRNAs是AD的潜在生物标志物。实时定量逆转录PCR(qRT-PCR)分析显示,与正常样本相比,AD血清样本中PART1下调,而SNHG14上调。本研究阐明了lncRNAs在AD发病机制中的作用,并提出了可用于设计AD诊断和治疗药物的新lncRNAs。