Microarray Profiling and Functional Identification of LncRNA in Mice Intestinal Mucosa Following Intestinal Ischemia/Reperfusion.
Microarray Profiling and Functional Identification of LncRNA in Mice Intestinal Mucosa Following Intestinal Ischemia/Reperfusion.
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DOI：
10.1016/j.jss.2020.08.066
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发表时间：
2020-10
期刊：
影响因子：
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通讯作者：
Miao Xu;Yong Yang;Qiwen Deng;Jian‐tong Shen;Wei-Feng Liu;Wen-jing Yang;Ke-xuan Liu
中科院分区：
文献类型：
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作者：
Miao Xu;Yong Yang;Qiwen Deng;Jian‐tong Shen;Wei-Feng Liu;Wen-jing Yang;Ke-xuan Liu
肠缺血-再灌注（intestinal ischemia-reperfusion，I/R）损伤是临床上常见的疾病，死亡率高，但其机制尚不清楚。虽然长链非编码RNA（lncRNA）最近已成为其他器官I/R损伤的关键分子，但其表达变化及其在肠I/R中的潜在作用尚不清楚。并通过基因本体（GO）和京都基因与基因组百科全书（KEGG）途径分析阐明了它们的生物学功能。然后，通过qRT-PCR进一步验证一些lncRNA。结果共检测到3602个异常表达的lncRNA（1503个上调，2099个下调）和3158个mRNA（1528个上调，1630个下调）。通过qRT-PCR验证了lncRNA AK 089510的过表达，CNC分析显示了其靶基因。AK 089510-siRNA可降低缺氧缺糖处理后肠上皮细胞Casp 6和Casp 7的表达，抑制肠上皮细胞凋亡。结论本研究揭示了肠I/R后小鼠肠黏膜lncRNA和mRNA的表达模式，并预测了其潜在的功能和途径。我们发现AK 089510是一种新的lncRNA，参与肠粘膜细胞凋亡，推进我们对肠I/R损伤的分子机制的理解。
BackgroundIntestinal ischemia-reperfusion (I/R) injury is a common clinical event with high mortality, but its mechanism is elusive. Although long noncoding RNAs (lncRNAs) have recently emerged as critical molecules in I/R damage in other organs, the changes in their expression and potential roles in intestinal I/R remain unclear.MethodsThe expression profiles of both lncRNAs and mRNAs in mouse intestinal mucosa after intestinal I/R were explored by a microarray approach, and their biological functions were elucidated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Then, some lncRNAs were further verified by qRT-PCR. Based on the coding-noncoding gene coexpression (CNC) network analyses, the role of lncRNA AK089510 in intestinal I/R-induced intestinal mucosa apoptosis was investigated by knockdown assayin vitro.ResultsA total of 3602 aberrantly expressed lncRNAs (1503 upregulated and 2099 downregulated) and 3158 mRNAs (1528 upregulated and 1630 downregulated) were identified. The dysregulated transcripts were enriched in the lipid metabolic process, apoptotic process, reactive oxygen species metabolic process, MAPK, TNF, ErbB, mTOR, and FoxO signaling pathways, and so on. The overexpression of lncRNA AK089510 was validated by qRT-PCR, and the CNC analysis revealed its target mRNAs. AK089510-siRNA reduced Casp6 and Casp7 expression and suppressed intestinal epithelial cell apoptosis after oxygen-glucose deprivation treatment.ConclusionsOur study revealed the lncRNA and mRNA expression patterns in mouse intestinal mucosa after intestinal I/R and predicted their potential functions and pathways. We identified AK089510 as a novel lncRNA involved in the apoptosis of intestinal mucosa, advancing our understanding of the molecular mechanisms of intestinal I/R injury.