Profile analysis reveals endogenous RNAs regulate necrotizing enterocolitis progression
Profile analysis reveals endogenous RNAs regulate necrotizing enterocolitis progression
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谱分析揭示内源性 RNA 调节坏死性小肠结肠炎进展
DOI：
10.1016/j.biopha.2020.109975
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Shuping Han
中科院分区：
文献类型：
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作者：
Yan Xu;Yiwen Liu;Hanying Xie;Yahui Zhou;Xiangyun Yan;Wenjuan Chen;Xingyun Wang;Zhangbin Yu;Fei Wang;Xiao-Hui Chen;Jun Wang;Shuping Han
坏死性小肠结肠炎（NEC）是早产儿最常见和最具破坏性的胃肠道疾病之一，其潜在机制尚不清楚。非编码RNA（ncRNA）在肠道疾病中起着关键作用;然而，对它们在NEC发展中的作用知之甚少。为了更深入地了解NEC的病理生理机制，在NEC大鼠模型中检测了长非编码RNA（lncRNA）、microRNA（miRNAs）和mRNA。NEC组中共有1820条lncRNAs、118条miRNAs和929条mRNAs差异表达。基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析表明这些分子在凋亡、自噬性细胞死亡、TLR 4信号通路、Notch信号通路和mTOR信号通路中富集。这些途径被认为与NEC密切相关。此外，lncRNA-miRNA相互作用网络的构建，和四个新的，差异表达的lncRNA与大的变化，随机验证使用定量聚合酶链反应（qPCR）。GO和KEGG通路分析表明，这4种lncRNA均与TLR 4信号通路和Notch信号通路的负调控有关。这些差异表达的lncRNA可能通过与miRNAs相互作用参与NEC的发生发展，并可能作为NEC的生物标志物和靶基因。
Necrotizing enterocolitis (NEC) is one of the most common and devastating gastrointestinal diseases in preterm newborns, and its underlying mechanisms remain unclear. Non-coding RNAs (ncRNAs) play critical roles in intestinal diseases; however, little is known about their roles in the development of NEC. To gain a deeper understanding of the pathophysiological mechanism of NEC, long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs were detected in an NEC rat model. In total, 1820 lncRNAs, 118 miRNAs and 929 mRNAs were differentially expressed in NEC group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these molecules were enriched in apoptosis, autophagic cell death, TLR4 signaling pathway, Notch signaling pathway, and mTOR signaling pathway. These pathways are thought to be closely associated with NEC. Furthermore, a lncRNA-miRNA interaction network was constructed, and four of the novel, differentially expressed lncRNAs with large changes were randomly verified using quantitative polymerase chain reaction (qPCR). The GO and KEGG pathway analysis of these four lncRNAs showed that they were associated with the negative regulation of TLR4 signaling pathway and Notch signaling pathway. In conclusion, our study revealed that these differentially expressed lncRNAs may participate in the development of NEC via interactions with miRNAs and may serve as possible biomarkers and target genes in NEC.