4.5 Article

Microarray Profiling and Functional Identification of LncRNA in Mice Intestinal Mucosa Following Intestinal Ischemia/Reperfusion

期刊

JOURNAL OF SURGICAL RESEARCH
卷 258, 期 -, 页码 389-404

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jss.2020.08.066

关键词

Intestine; Ischemia; reperfusion injury; Long noncoding RNA; Microarray; Apoptosis

类别

资金

  1. National Natural Science Foundation of China [81671955]
  2. Science and Technology Foundation of Guangdong province [2014A020212660]

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This study identified the expression patterns of lncRNAs and mRNAs in mouse intestinal mucosa after intestinal I/R, and predicted their potential functions and pathways. AK089510 was identified as a novel lncRNA involved in the apoptosis of intestinal mucosa, advancing the understanding of the molecular mechanisms of intestinal I/R injury.
Background: Intestinal 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. Methods: The 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 codingnoncoding gene coexpression (CNC) network analyses, the role of lncRNA AK089510 in intestinal I/R-induced intestinal mucosa apoptosis was investigated by knockdown assay in vitro. Results: A total of 3602 aberrantly expressed lncRNAs (1503 upregulated and 2099 down regulated) 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. Conclusions: Our 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. (C) 2020 Elsevier Inc. All rights reserved.

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