Comprehensive Analysis of Hub Genes Associated With Competing Endogenous RNA Networks in Stroke Using Bioinformatics Analysis

Chen, Xiuqi; Wu, Danhong

doi:10.3389/fgene.2021.779923

Cited by 5 publications

(14 citation statements)

References 69 publications

(82 reference statements)

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“…IS remains a leading cause of permanent disability and causes tremendous burden on human health and the economy [13]. Despite remarkable advances in the development of therapeutic and rehabilitation strategies, treatment e cacy remains unsatisfactory, and a considerable number of patients continue to suffer from long-term disability [10].…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidence points to biomarkers as playing a crucial role in the pathogenesis, prognosis, and treatment of stroke [20]. Both in vitro and in vivo studies have found that the abnormal expression of RNAs can be used as biomarkers for IS through sequencing analysis [2,6,13]. Therefore, identifying biomarkers and developing effective targeted molecular therapies will greatly increase the opportunity for patients to receive effective post-stroke rehabilitation [13].…”

Section: Discussionmentioning

confidence: 99%

“…Both in vitro and in vivo studies have found that the abnormal expression of RNAs can be used as biomarkers for IS through sequencing analysis [2,6,13]. Therefore, identifying biomarkers and developing effective targeted molecular therapies will greatly increase the opportunity for patients to receive effective post-stroke rehabilitation [13]. In our study, seven groups of RNA-sequencing results were combined to construct a ceRNA network through a comprehensive analysis.…”

Section: Discussionmentioning

confidence: 99%

“…The data were quantile normalized, and the differential expressed miRNAs (DEmiRNAs), mRNAs (DEmRNAs), and lncRNAs (DElncRNAs) between the IS and control samples were identi ed using R's limma package (v3.52.0) [19]. The P < 0.05, |log 2 fold change (FC)| > 0.5 were selected as cut-off criteria in identifying DEmRNAs and DEmiRNAs by previously reported methods [9,13], and |log 2 fold change (FC)| >1 were selected to identify DElncRNA [20,21]. Thereafter, volcano plots of DEmiRNAs, DElncRNAs, and DEmRNAs were generated using the ggplot2 package (v3.3.6) [22].…”

Section: Differential Expression Analysismentioning

confidence: 99%

“…Long non-coding RNAs (lncRNAs) are also a kind of non-coding RNA with more than 200 nucleotides in length that regulate target gene expression by interacting directly with mRNAs as a transcriptional regulator, or by acting as competing endogenous RNAs (ceRNAs), for miRNAs [13,14] and have been implicated in the development of IS [2,15].…”

Section: Introductionmentioning

confidence: 99%

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Competing Endogenous RNA Network Analysis of the Molecular Mechanisms of Ischemic Stroke

Chen

et al. 2022

Preprint

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Object Through the construction of a competing endogenous RNA (ceRNA) network, this study aimed to search for and investigate the possible molecular mechanisms of potential biomarkers associated with ischemic stroke (IS). Method Seven expression profiles of miRNA, mRNA, and lncRNA were downloaded from the NCBI GEO database. Following the exploration of the differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs), and mRNAs (DEmRNAs), the lncRNA–miRNA and miRNA–mRNA pairs were predicted with target prediction tools, and a ceRNA network was constructed. Subsequently, functional enrichment analyses were performed, a protein–protein interaction (PPI) network was constructed, and the immune cell infiltration landscapes were evaluated using the CIBERSORT algorithm. Finally, we identified the key lncRNAs, miRNAs, and mRNAs of IS using bioinformatics methods and assessed their diagnostic efficacy in the validation datasets. The expression of these key genes was also validated using the quantitative real-time polymerase chain reaction (qRT-PCR) in PC12 cells. Results We constructed the ceRNA network for IS. The DEmRNAs were mainly enriched in inflammatory signaling pathways through enrichment analysis. In the cerebral infarction group, the B cells naïve, T cells naïve, and monocytes had statistically different numbers compared with the control group. We used the criterion AUC > 0.7 to screen key miRNAs, mRNAs, and lncRNA. Finally, six key RNAs were identified. The verification results of the relative RNA expression by qRT-PCR were consistent with the results of the bioinformatics analysis. Conclusion Our results suggest that the ceRNA network exerted an important role in the inflammatory pathogenesis of IS and provided a new strategy to conduct IS research.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Differential Expression Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Competing Endogenous RNA Network Analysis of the Molecular Mechanisms of Ischemic Stroke

Chen

et al. 2022

Preprint

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Integrated Microarray Analysis to Identify Genes and Small-Molecule Drugs Associated with Stroke Progression

Cui¹,

Zhao

Huang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Several blood biomarkers are now considered increasingly important for stratifying risk, monitoring disease progression, and evaluating the response to therapy in ischemic stroke. The purpose of the present study was to identify the key genes associated with ischemic stroke progression and elucidate the potential therapeutic small molecules. Microarray datasets related to stroke for GSE58294, GSE22255, and GSE16561 were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were filtered using the Limma package. DAVID was then searched to perform gene ontology (GO) and pathway enrichment analyses. Based on the DEGs, a protein-protein interaction (PPI) network was developed using Cytoscape, and MCODE was applied to conduct module analysis. Finally, to identify the potential drugs for ischemic stroke, the connectivity map (CMap) database was used. Sixty DEGs were identified after analyzing the three datasets. The GO data analysis revealed that the DEGs were significantly associated with biological processes, including positive regulation of programmed cell death, protein localization in organelles, and positive regulation of apoptosis. KEGG analysis showed that the DEGs were particularly enriched in the Fc epsilon RI signaling pathway, MAPK signaling pathway, and Huntington’s disease. We selected five DEGs with high connectivity (CYBB, SYK, DUSP1, TNF, and SP1) that significantly predicted stroke progression. In addition, CMap prediction showed ten small molecules that could be used as adjuvants when treating ischemic stroke. The outcomes of the present study indicated that the five genes mentioned above can be considered potential targets for developing new medications that can modify the ischemic stroke process, and mycophenolic acid was the most promising small molecule to treat ischemic stroke.

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

Chen

Yang

et al. 2023

BMC Genomics

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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.

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Comprehensive Analysis of Hub Genes Associated With Competing Endogenous RNA Networks in Stroke Using Bioinformatics Analysis

Cited by 5 publications

References 69 publications

Competing Endogenous RNA Network Analysis of the Molecular Mechanisms of Ischemic Stroke

Competing Endogenous RNA Network Analysis of the Molecular Mechanisms of Ischemic Stroke

Integrated Microarray Analysis to Identify Genes and Small-Molecule Drugs Associated with Stroke Progression

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

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