MicroRNAs (miRNAs) are reported to play pivotal roles in reactive oxygen species (ROS)-induced endothelial cell injury and several studies have demonstrated the miRNA distribution in the mitochondria of various cells. However, very little is known about its changes and roles in ROS-induced endothelial cell injury. In the present study, we systematically revealed the distribution changes of miRNAs in mitochondria during ROS-induced endothelial cell injury and found that H2O2 obviously reduced the mitochondrial distribution of many miRNAs without affecting their expression levels in the whole endothelial cells. Most of these miRNAs showing reduced mitochondrial distribution were potentially involved in ROS-induced endothelial cell injury. MiR-381-3p was a typical representative of these miRNAs and its redistribution between mitochondria and cytosol regulated the network consisting of downstream molecules (P53, P21, CCND1, and MYC) by inhibiting its target genes (LRP6 and NFIA) to promote apoptosis and inhibit proliferation in endothelial cells. Our findings highlight the significance of redistribution of miRNAs between mitochondria and cytosol and improve our understanding of miRNA function regulation.
Keywords: Endothelial cell injury; Mitochondrial distribution; Reactive oxygen species; miRNA.
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