Protective Effect of Quercetin against H2O2-Induced Oxidative Damage in PC-12 Cells: Comprehensive Analysis of a lncRNA-Associated ceRNA Network

Abstract

Quercetin is a bioflavonoid with potential antioxidant properties. However, the mechanisms underlying its effects remain unclear. Herein, we focused on integrating long noncoding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) sequencing of PC-12 cells treated with quercetin. We treated PC-12 cells with hydrogen peroxide to generate a validated oxidative damage model. We evaluated the effects of quercetin on PC-12 cells and established the lncRNA, miRNA, and mRNA profiles of these cells. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of these RNAs were conducted to identify the key pathways. Quercetin significantly protected PC-12 neuronal cells from hydrogen peroxide-induced death. We identified 297, 194, and 14 significantly dysregulated lncRNAs, miRNAs, and mRNAs, respectively, associated with the antioxidant effect of quercetin. Furthermore, the phosphatidylinositol-3-kinase/protein kinase B pathway was identified as the crucial signalling pathway. Finally, we constructed a lncRNA-associated competing endogenous RNA (ceRNA) network by utilizing oxidative damage mechanism-matched miRNA, lncRNA, and mRNA expression profiles and those changed by quercetin. In conclusion, quercetin exerted a protective effect against oxidative stress-induced damage in PC-12 cells. Our study provides novel insight into ceRNA-mediated gene regulation in the progression of oxidative damage and the action mechanisms of quercetin.