Differential microRNA profiling in a cellular hypoxia reoxygenation model upon posthypoxic propofol treatment reveals alterations in autophagy signaling network

Oxid Med Cell Longev. 2013:2013:378484. doi: 10.1155/2013/378484. Epub 2013 Dec 22.

Abstract

Recent studies indicate that propofol may protect cells via suppressing autophagic cell death caused by excessive reactive oxygen species induced by hypoxia reoxygenation (H/R). It is established that gene expression patterns including autophagy-related genes changed significantly during the process of H/R in the presence or absence of propofol posthypoxia treatment (P-PostH). The reasons for such differences, however, remain largely unknown. MicroRNAs provide a novel mechanism for gene regulation. In the present study, we systematically analyzed the alterations in microRNA expression using human umbilical vein endothelial cells (HUVECs) subjected to H/R in the presence or absence of posthypoxic propofol treatment. Genome-wide profiling of microRNAs was then conducted using microRNA microarray. Fourteen miRNAs are differentially expressed and six of them were validated by the quantitative real-time PCR (Q-PCR) of which three were substantially increased, whereas one was decreased. To gain an unbiased global perspective on subsequent regulation by altered miRNAs, predicted targets of ten miRNAs were analyzed using the Gene Ontology (GO) analysis to build signaling networks. Interestingly, six of the identified microRNAs are known to target autophagy-related genes. In conclusion, our results revealed that different miRNA expression patterns are induced by propofol posthypoxia treatment in H/R and the alterations in miRNA expression patterns are implicated in regulating distinctive autophagy-related gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / drug effects
  • Autophagy / genetics*
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Gene Expression Profiling*
  • Gene Expression Regulation / drug effects
  • Gene Regulatory Networks
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Models, Biological*
  • Oligonucleotide Array Sequence Analysis
  • Oxygen / pharmacology*
  • Propofol / pharmacology*
  • Reproducibility of Results
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*

Substances

  • MicroRNAs
  • Oxygen
  • Propofol