Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Biomed Res Int. 2018 Jan 8;2018:8354350. doi: 10.1155/2018/8354350. eCollection 2018.
Although extensive studies have identified large number of microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in ischemic stroke, the RNA regulation network response to focal ischemia remains poorly understood. In this study, we simultaneously interrogate the expression profiles of lncRNAs, miRNAs, and mRNAs changes during focal ischemia induced by transient middle cerebral artery occlusion. A set of 1924 novel lncRNAs were identified and may involve brain injury and DNA repair as revealed by coexpression network analysis. Furthermore, many short interspersed elements (SINE) mediated lncRNA:mRNA duplexes were identified, implying that lncRNAs mediate Staufen1-mediated mRNA decay (SMD) which may play a role during focal ischemia. Moreover, based on the competitive endogenous RNA (ceRNA) hypothesis, a stroke regulatory ceRNA network which reveals functional lncRNA:miRNA:mRNA interactions was revealed in ischemic stroke. In brief, this work reports a large number of novel lncRNAs responding to focal ischemia and constructs a systematic RNA regulation network which highlighted the role of ncRNAs in ischemic stroke.
尽管大量研究已经确定了大量的 microRNAs(miRNAs)和长非编码 RNA(lncRNAs)在缺血性中风中,但对局部缺血引起的 RNA 调控网络反应仍知之甚少。在这项研究中,我们同时研究了短暂性大脑中动脉闭塞诱导的局部缺血过程中 lncRNAs、miRNAs 和 mRNAs 变化的表达谱。一组 1924 个新的 lncRNAs 被鉴定出来,可能涉及脑损伤和 DNA 修复,如共表达网络分析所示。此外,还鉴定了许多短散布元件(SINE)介导的 lncRNA:mRNA 双链体,这表明 lncRNA 介导 Staufen1 介导的 mRNA 降解(SMD),这可能在局部缺血中起作用。此外,基于竞争性内源性 RNA(ceRNA)假说,揭示了缺血性中风中功能性 lncRNA:miRNA:mRNA 相互作用的中风调控 ceRNA 网络。总之,这项工作报道了大量新的 lncRNAs 对局部缺血的反应,并构建了一个系统的 RNA 调控网络,突出了 ncRNAs 在缺血性中风中的作用。