在自闭症中对长非编码RNAs调节失调和突触相关的ceRNA调节轴的综合分析
Miaomiao Jiang1, Ziqi Wang2,3, Tianlan Lu1
1National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, China.
Translational psychiatry
|December 6, 2023
概括
长非编码RNA (lncRNA) MIR600HG失调与自闭症谱系障碍 (ASD) 有关. 这种新型灵长类动物特异性的lncRNA会影响miRNA-mRNA网络,可能会影响ASD发展中的突触发生.
科学领域:
- 神经发育障碍 神经发育障碍
- 遗传学和基因组学 在
- 分子生物学分子生物学
背景情况:
- 自闭症谱系障碍 (ASD) 是一种复杂的神经发育障碍,主要是未知的长非编码RNA (lncRNA) 功能.
- 基因网络分析提供了一种强大的方法来解开复杂的疾病机制.
研究的目的:
- 通过使用综合的多omics数据,研究 lncRNAs 在自闭症谱系障碍 (ASD) 中的作用.
- 确定特定的lncRNA及其与ASD病原发生相关的调节网络.
主要方法:
- 在5个人类死后大脑数据集中对RNA表达,全外体测序,基因共表达网络和蛋白质-蛋白质相互作用进行综合分析.
- 通过整合lncRNAs,microRNAs (miRNAs) 和信使RNAs (mRNAs) 来构建一个竞争的内源RNA (ceRNA) 网络.
- 机器学习算法 (支持矢量机,随机森林) 用于生物标记物识别.
主要成果:
- 388个lncRNA和5个共同表达模块被发现在ASD中发生了变化,M4模块与ASD有显著的相关性,并且在突触信号通路中得到了丰富.
- MIR600HG是一种灵长类动物特有的lncRNA,在ASD脑组织和外围血液中被降低调节,与9种自闭症相关的miRNA相互作用.
- MIR600HG的淘汰导致突触相关的mRNAs的下调,一个诊断模型实现了0.851.85的AUC.
结论:
- MIR600HG是一种在ASD中显著失调的新型lncRNA,有助于ASD相关的miRNA-mRNA调节轴.
- MIR600HG失调可能在自闭症谱系障碍中观察到的突触发生变化中发挥关键作用.
- 这项研究强调MIR600HG作为潜在的诊断标志物和ASD治疗点.
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