Study and Characterization of Long Non-coding RUNX1-IT1 among Large Artery Atherosclerosis Stroke Patients Based on the ceRNA Hypothesis

Recent studies have shed light on the involvement of long non-coding RNAs (lncRNAs) in the initiation and development of stroke. However, the regulatory function of many lncRNAs in large artery atherosclerosis (LAA) has not been fully elucidated. Based on the competing endogenous RNA (ceRNA) hypothesis recently proposed by Pandolfi, the present study was conducted using experimental techniques and bioinformatics to investigate the expression and regulatory function of a lncRNA involved in the development of LAA. The lncRNAs differentially expressed in stroke were obtained using meta-analysis, and one lncRNA was selected for experimental studies on patients with LAA (n = 100) and healthy controls (n = 100) using quantitative real-time polymerase chain reaction (qRT-PCR). The patients were also evaluated through meta-analysis to identify the function of the selected lncRNA, miRNAs, and mRNAs with altered expression in stroke. Finally, the experimental results and meta-analysis findings were integrated, and different functional groups were assigned. The results indicated that the level of lncRNA-RUNX1-IT1 was significantly lower in the patients with LAA compared to the healthy control subjects (p > 0.05). Logistic regression analyses revealed that the expression of lncRNA-RUNX1-IT1 was inversely correlated with LAA (P = 009, OR = 0.871, 95% CI: 0.786-0.965). In addition, a network of differentially expressed genes (DE genes) was created for miRNAs and mRNAs based on their association with lncRNA-RUNX1-IT1. Functional analysis showed that the DE genes in the network are involved in the apoptosis and alternative splicing of RNAs. The findings of the present study suggest that the downregulation of lncRNA-RUNX1-IT1 is associated with LAA development by interrupting the regulatory network of cells. The results of network analysis demonstrated that the lncRNA-RUNX1-IT1 could influence the expression of mRNAs and miRNAs involved in the apoptosis and alternative splicing of RNAs.