Department of Pediatrics, The Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, 210004, China; The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002. China.
Department of Pediatrics, The Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, 210004, China.
Biomed Pharmacother. 2020 May;125:109975. doi: 10.1016/j.biopha.2020.109975. Epub 2020 Feb 7.
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.
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,但其潜在机制尚不清楚。非编码 RNA(ncRNA)在肠道疾病中发挥着关键作用;然而,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)、microRNAs(miRNA)和信使 RNA(mRNA)。在 NEC 组中,共有 1820 个 lncRNA、118 个 miRNA 和 929 个 mRNA 表达差异。基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析表明,这些分子富集在细胞凋亡、自噬性细胞死亡、TLR4 信号通路、Notch 信号通路和 mTOR 信号通路。这些通路被认为与 NEC 密切相关。此外,构建了 lncRNA-miRNA 相互作用网络,并使用实时定量聚合酶链反应(qPCR)随机验证了四个具有大变化的新型差异表达 lncRNA。这四个 lncRNA 的 GO 和 KEGG 通路分析表明,它们与 TLR4 信号通路和 Notch 信号通路的负调控有关。总之,我们的研究表明,这些差异表达的 lncRNA 可能通过与 miRNA 的相互作用参与 NEC 的发生,并且可能作为 NEC 中的潜在生物标志物和靶基因。