Construction of lncRNA-Mediated ceRNA Network for Investigating Immune Pathogenesis of Ischemic Stroke

Ischemic stroke (IS) is a common and serious neurological disease. Extensive evidence indicates that activation of the immune system contributes significantly to the development of IS pathology. In recent years, some long non-coding RNAs (lncRNAs), acting as competing endogenous RNAs (ceRNAs), have been reported to affect IS process, especially the immunological response after stroke. However, the roles of lncRNA-mediated ceRNAs in immune pathogenesis of IS are not systemically investigated. In the present study, we generated a global immune-related ceRNA network containing immune-related genes (IRGs), miRNAs, and lncRNAs based on experimentally verified interactions. Further, we excavated an IS immune-related ceRNA (ISIRC) network through mapping significantly differentially expressed IRGs, miRNAs, and lncRNAs of patients with IS into the global network. We analyzed the topological properties of the two networks, respectively, and found that lncRNA NEAT1 and lncRNA KCNQ1OT1 played core roles in aforementioned two immune-related networks. Moreover, the results of functional enrichment analyses revealed that lncRNAs in the ISIRC network were mainly involved in several immune-related biological processes and pathways. Finally, we identified 17 lncRNAs which were highly related to the immune mechanism of IS through performing random walk with restart for the ISIRC network. Importantly, it has been confirmed that NEAT1, KCNQ1OT1, GAS5, and RMRP could regulate immuno-inflammatory response after stroke, such as production of inflammatory factors and activation of the immune cells. Our results suggested that lncRNAs exerted an important role in the immune pathogenesis of IS and provided a new strategy to do research on IS.