Identification of Differentially Expressed Long Noncoding RNAs in Mice Intestines After Severe Burns and a Preliminary Study into the Key Gene H19

J Burn Care Res. 2022 Jan 5;43(1):16-29. doi: 10.1093/jbcr/irab017.

Abstract

The intestine is considered the key organ in stress response to severe burns and injury to the intestine after severe burns can be fatal. However, the injury and subsequent repair of intestinal tissues after severe burns at the genetic level are poorly understood. Long noncoding RNAs (lncRNAs) have important functions in regulating many biological processes, including gene transcription and translation. Autophagy is a process of intracellular degradation and reutilization of cytoplasmic proteins and organelles. We herein analyzed the genome-wide expression profile of lncRNAs and mRNAs after severe burns in the intestines of mice by lncRNA microarray. Quantitative reverse transcription-polymerase chain reaction was performed to verify the reliability of microarray analysis results, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used for bioinformatics analysis of differentially expressed mRNAs. The common regulatory network between the top 10 differentially expressed lncRNAs and trans-related mRNAs were visualized by Cytoscape (v3.7.2). Next, we hypothesized that H19 is the key gene for intestinal mucosal repair. After H19 was overexpressed, the changes in downstream autophagy protein expression levels were observed. GO and KEGG analysis indicated that the differentially expressed mRNAs were mainly enriched in a cell cycle- and mitosis-related genes. Overexpression of lncRNA-H19 showed that the autophagy-related gene Trim21 was upregulated, while HIF1α was downregulated. LncRNA-H19 played a key role in repairing the intestinal mucosa, and overexpression of lncRNA-H19 activated autophagy and migration of intestinal epithelial cells (IEC-6).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Burns / metabolism*
  • Genome-Wide Association Study
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Intestines / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microarray Analysis
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / metabolism
  • Ribonucleoproteins / metabolism

Substances

  • H19 long non-coding RNA
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Long Noncoding
  • RNA, Messenger
  • Ribonucleoproteins
  • SS-A antigen