Competing endogenous RNA network analysis of the molecular mechanisms of ischemic stroke

Abstract

Background Ischemic stroke (IS) is a serious neurological disease that largely results in long-term disability and death. Extensive evidence has indicated that the activation of inflammation and ferroptosis significantly contribute to the development of IS pathology. However, the underlying molecular mechanism remains unclear. In this study, we aimed to identify potential biomarkers associated with IS through the construction of a competing endogenous RNA (ceRNA) network and to investigate the possible inflammatory and ferroptosis-related molecular mechanisms. Results We identified 178 differentially expressed target messenger RNAs (DETmRNAs) associated with IS. As revealed through enrichment analysis, the DEmRNAs were mainly enriched in the inflammatory signaling pathways and also related to ferroptosis mechanism. The CIBERSORT algorithm showed immune infiltration landscapes in which the naïve B cells, naïve T cells, and monocytes had statistically different numbers in the cerebral infarction group compared with the control group. A ceRNA network was constructed in this study involving 44 long non-coding RNAs (lncRNAs), 15 microRNAs (miRNAs), and 160 messenger RNAs (mRNAs). We used the receiver operating characteristic (ROC) analysis to identify three miRNAs (miR-103a-3p, miR-140-3p, and miR-17-5p), one mRNA (TLR4), and one lncRNA (NEAT1) as the potential key biomarkers of the ceRNA network. The key mRNA and lncRNA were shown to be highly related to the ferroptosis mechanism of IS. The expression of these key biomarkers was also further validated by a method of quantitative real-time polymerase chain reaction in SH-SY5Y cells, and the validated results were consistent with the findings predicted by bioinformatics. Conclusion Our results suggest that the ceRNA network may exert an important role in the inflammatory and ferroptosis molecular mechanisms of IS, providing new insight into therapeutic IS targets.

MiR-122 overexpression alleviates oxygen–glucose deprivation-induced neuronal injury by targeting sPLA2-IIA

“…Possessing high stability in human fluids, miRNAs are promising biomarkers for disease diagnosis and prognosis. Additionally, miRNA-based therapeutics hold the potential to revolutionize the treatment of diverse human pathologies (14,36,37). Emerging evidence suggests that miRNA expression is upregulated during stroke and is crucial in regulating the prognosis of stroke patients (21,28).…”

“…MicroRNAs (miRNAs) comprise a group of small RNAs that are highly conserved, endogenous, non-coding and widely distributed across eukaryotes. They function primarily in the post-transcriptional regulation of gene expression (14,15). An expanding body of evidence underscores that miRNAs play a crucial role in the pathophysiology of IS.…”

Exploration of the biomarkers of comorbidity of psoriasis with inflammatory bowel disease and their association with immune infiltration

“…The package “limma” and “sva” of R software (version 4.2.3) was utilized to preprocess and perform batch effect correction when merging the datasets, and Principal Components Analysis (PCA) plots was constructed to evaluate the effect on correction. 19 …”

Multicenter Validation of lncRNA and Target mRNA Diagnostic and Prognostic Biomarkers of Acute Ischemic Stroke From Peripheral Blood Leukocytes

“… 14 Most studies focusing on single lncRNA lack evidence from other blood components. Although accumulative bioinformatics analyses 15 , 16 and experiments in vitro and in vivo 17 , 18 , 19 , 20 have stressed the importance of using lncRNA‐related networks as biomarkers, there is still a lack of internal and external validation and model improvement reports in human studies.…”