Construction of a long non-coding RNA-mediated transcription factor and gene regulatory triplet network reveals global patterns and biomarkers for ischemic stroke

摘要

Ischemic stroke (IS) is a severe neurological disease and a major cause of death and disability throughout the world. A long non-coding (lnc)RNA, transcription factor (TF) and gene can form a lncRNA-mediated regulatory triplet (LncMRT), which is a functional network motif that regulates numerous aspects of human diseases. However, systematic identification and molecular characterization of LncMRTs and their roles in IS has not been carried out. In the present study, a global LncMRT network was constructed and the topological features were characterized based on experimentally verified interactions. An integrated approach was developed to identify significantly dysregulated LncMRTs in peripheral blood mononuclear cells of IS and these dysregulated LncMRT networks exhibited specific topological characteristics and a closer network structure than the global LncMRT network that was constructed. The variation of the risk score for LncMRTs indicated that there were multiple dysregulated patterns of LncMRTs in IS. Numerous core clusters were identified from dysregulated LncMRT networks and these core clusters could distinguish IS patient and matched control samples. Finally, functional analyses demonstrated that LncMRTs associated with IS participated in the regulation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. In conclusion, the roles of the LncMRTs in IS were elucidated, which could be beneficial for understanding IS pathogenesis and treatment.