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Identifying Autophagy-Related lncRNAs and Potential ceRNA Networks in NAFLD

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease with complex pathogenesis, which brings economic burden to the society, and there is still no effective therapy. Impaired autophagy has been implicated in the development of NAFLD. Long noncoding RNAs (lncRNAs) are also reported to play a role in the pathogenesis of NAFLD. However, the role of autophagy-related lncRNAs in NAFLD disease has not been elucidated. Here, we mined GSE135251, GSE160016, GSE130970 and GSE185062 datasets from the Gene Expression Omnibus database (GEO) and obtained the human autophagy-related gene list from the Human Autophagy Database (HADb) for in-depth bioinformatic analysis. Following differential expression analysis and intersection of the datasets, Pearson correlation analysis was performed on DElncRNAs and autophagy-related DEmRNAs to obtain autophagy-related lncRNAs, and then Starbase3.0 and TargetScan7.2 were used to construct competing endogenous RNAs (ceRNA) regulatory networks. We constructed four lncRNA-dominated ceRNA regulatory networks (PSMG3-AS1, MIRLET7BHG, RP11-136K7.2, LINC00925), and visualized with Cytoscape. Then we performed co-expression analysis of the ceRNA networks and autophagy-related genes, and functionally annotated them with Metascape. Finally, we performed receiver operating characteristic curve (ROC) analysis on lncRNAs and mRNAs within the ceRNA networks. Conclusively, our project is the first to study autophagy-related lncRNAs in NAFLD and finally mined four autophagy-related lncRNAs (PSMG3-AS1, MIRLET7BHG, RP11-136K7.2, LINC00925). We suggested that the four autophagy-related lncRNAs may be closely associated with the occurrence and development of NAFLD through the corresponding ceRNA regulatory networks. This research brings new horizons to the study of NAFLD.

SUBMITTER: Cao Z

PROVIDER: S-EPMC9279897 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundJuvenile spondyloarthropathies (JSpA) are defined as a heterogeneous group of diseases that start before the age of 16. The study aimed to identify key genes and pathways that are influenced by circRNAs and to screen potential therapeutic agents for JSpA. The study involved the analysis of circRNA expression profiles, identification of circRNA-miRNA-mRNA regulatory networks, and functional annotation of differentially expressed genes. The results of the study may have provided insights into the molecular mechanisms underlying JSpA and potential therapeutic targets for this disease.MethodsIn this study, sequencing data of circRNA, miRNA, and mRNA were obtained from the GEO datasets. The data were then analyzed to identify candidates for constructing a circRNA-miRNA-mRNA network based on circRNA-miRNA interactions and miRNA-mRNA interactions. Functional enrichments of genes were performed using the DAVID database. A PPI network was constructed using the STRING database and visualized using Cytoscape software. The MCODE plugin app was used to explore hub genes in the PPI network. The expression changes in immune cells were assessed using the online CIBERSORT algorithm to obtain the proportion of various types of immune cells. Finally, the Connectivity Map L1000 platform was used to identify potential agents for JSpA treatment. Overall, this study aimed to provide a comprehensive understanding of the molecular mechanisms underlying JSpA and to identify potential therapeutic agents for this disease.ResultsA total of 225 differentially expressed circRNAs (DEcircRNAs), 23 differentially expressed miRNAs (DEmiRNAs) and 1324 differentially expressed mRNAs (DEmRNAs) were identified. We integrated 5 overlapped circRNAs, 7 miRNAs and 299 target mRNAs into a circRNA-miRNA-mRNA network. We next identified 10 hub genes based on the PPI network. KEGG pathway analysis revealed that the DEGs were mainly associated with JAK-STAT signal pathway. We found that neutrophils accounted for the majority of all enriched cells. In addition, we discovered several chemicals as potential treatment options for JSpA.ConclusionsThrough this bioinformatics analysis, we suggest a regulatory role for circRNAs in the pathogenesis and treatment of JSpA from the view of a competitive endogenous RNA (ceRNA) network.

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Identifying Autophagy-Related lncRNAs and Potential ceRNA Networks in NAFLD

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