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lncRNA-mRNA 网络的综合分析揭示了坏死性小肠结肠炎潜在的发生机制。

Integrated analysis of a lncRNA‑mRNA network reveals a potential mechanism underlying necrotizing enterocolitis.

机构信息

Department of Neonatology, Wuxi Children's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.

出版信息

Mol Med Rep. 2020 Jul;22(1):423-435. doi: 10.3892/mmr.2020.11083. Epub 2020 Apr 21.

Abstract

Previous studies have shown that long non‑coding RNAs (lncRNAs) serve important roles in necrotizing enterocolitis (NEC). However, the underlying mechanisms remain largely unknown. In order to examine the potential role of lncRNAs in NEC, the present study investigated lncRNA and mRNA expression profiles in NEC lesions and adjacent intestinal tissues using Next Generation Sequencing. A total of 4,202 differentially expressed lncRNAs (fold‑change >2; P<0.05) and 7,860 differentially expressed mRNAs (fold‑change >2; P<0.05) were identified. Moreover, 5 dysregulated lncRNAs and 5 mRNAs were randomly selected, and further assessed by reverse transcription‑quantitative PCR in vitro. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses demonstrated that the differentially expressed lncRNAs were closely associated with NEC, and were enriched in 'inflammatory response', 'Toll‑like receptor binding', 'PPAR signaling pathway', 'PI3K‑Akt signaling pathway', 'transforming growth factor‑β signaling pathway' and 'hypoxia‑inducible factor 1 signaling pathway'. In addition, co‑expression analysis demonstrated that these lncRNAs, including lncRNA ENST00000623580, lncRNA NONHSAT180418.1, lncRNA NONHSAT125636.2 and NONHSAT087855.2, may mediate the pathogenesis and development of NEC via lncRNA‑mRNA network interactions. Therefore, the present study provided a novel insight into the role of lncRNAs in NEC.

摘要

先前的研究表明,长非编码 RNA(lncRNA)在坏死性小肠结肠炎(NEC)中发挥重要作用。然而,其潜在的机制仍知之甚少。为了研究 lncRNA 在 NEC 中的潜在作用,本研究使用下一代测序技术,检测了 NEC 病变和相邻肠组织中的 lncRNA 和 mRNA 表达谱。共鉴定到 4202 个差异表达的 lncRNA(fold-change>2;P<0.05)和 7860 个差异表达的 mRNA(fold-change>2;P<0.05)。此外,随机选择了 5 个失调的 lncRNA 和 5 个 mRNA,并在体外通过逆转录-定量 PCR 进一步评估。基因本体论和京都基因与基因组百科全书分析表明,差异表达的 lncRNA 与 NEC 密切相关,并且富集于“炎症反应”、“Toll 样受体结合”、“PPAR 信号通路”、“PI3K-Akt 信号通路”、“转化生长因子-β信号通路”和“缺氧诱导因子 1 信号通路”。此外,共表达分析表明,这些 lncRNA,包括 lncRNA ENST00000623580、lncRNA NONHSAT180418.1、lncRNA NONHSAT125636.2 和 NONHSAT087855.2,可能通过 lncRNA-mRNA 网络相互作用介导 NEC 的发病机制和发展。因此,本研究为 lncRNA 在 NEC 中的作用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6564/7248486/8a33c027ddbd/MMR-22-01-0423-g00.jpg

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