ceRNA network analysis reveals the molecular mechanism by which umbilical cord mesenchymal stem cells reverse thymic epithelial cell senescence

Abstract:Background: A decreased number of thymic epithelial cells and the development of dysfunction of this population have been reported to be important factors in thymic degeneration, which can lead to thymus degeneration, proliferation defects and peripheral T-cell dysfunction. Previous research showed that umbilical cord mesenchymal stem cells can restore the structure and function of the aging thymus in vivo, but the specific mechanism is still unclear.Methods: We treated thymic epithelial cells with H₂O₂ to establish a cellular senescence model. We assessed the effect of umbilical cord mesenchymal stem cells on thymic epithelial cells and investigated the lncRNA, miRNA and mRNA profiles of these cells. Gene Ontology and Kyoto Genome Encyclopedia analyses were performed on these RNAs to identify key pathways.Results: Umbilical cord mesenchymal stem cells significantly reversed the H₂O₂-induced senescence of thymic epithelial cells. We identified 172 differentially expressed lncRNAs, 23 differentially expressed miRNAs and 272 differentially expressed mRNAs associated with the reversal of thymic epithelial senescence by umbilical cord mesenchymal stem cells. In addition, the PI3K-Akt signaling pathway was identified as a key signaling pathway that promotes cell proliferation by regulating the cell cycle. Finally, we constructed a lncRNA-associated competing endogenous RNA (ceRNA) network using matched miRNA, lncRNA, and mRNA expression profiles in the model dataset and altered miRNA expression profiles in umbilical cord mesenchymal stem cells.Conclusion: Umbilical cord mesenchymal stem cells have a protective effect against H2O2-induced thymic epithelial cell senescence. Our study provides new insights into the ceRNA-mediated gene regulation of thymic senescence progression and the mechanism of action of umbilical cord mesenchymal stem cells.