Dataset Information

Comprehensive Analysis of circRNA-Mediated ceRNA Regulatory Networks in relation to Recurrent Implantation Failure.

ABSTRACT: Recurrent implantation failure (RIF) is attributed to endometrial receptivity dysfunction with many unanswered questions. Up to now, there is no explanation for RIF, and therapeutic strategies are usually limited to supportive care. In this study, we differentially analyzed the raw data deposited in three eligible microarray datasets, GSE111974, GSE121219, and GSE147442 to screen DE-mRNAs, DE-miRNAs, and DE-circRNAs, respectively. The value of log2-fold change |log2FC| ≥ 1 and the adjusted p value < 0.05 were considered differentially expressed between RIF and fertile control. We found 350 DE-mRNAs, 43 DE-miRNAs, and 1968 DE-circRNAs between RIF and fertile control. The PPI network identified 6 hub genes with degree ≥10, KDR, AGT, POSTN, TOP2A, RRM2, and PTGS2, in RIF. KDR, AGT, POSTN, TOP2A, and RRM2 were downregulated in endometrial tissue samples of RIF compared with those of fertile control, while PTGS2 was upregulated in endometrial tissue samples of RIF compared with those of fertile control. According to the ceRNA hypothesis, 15 groups of ceRNA network based on 10 circRNAs, hsa_circ_001572, hsa_circ_001884, hsa_circ_001375, hsa_circ_001449, hsa_circ_000029, hsa_circ_001168, hsa_circ_000210, hsa_circ_001484, hsa_circ_001698, and hsa_circ_000089 were constructed in RIF. In conclusion, the present study examined the possible role of circRNAs and their related ceRNA network involved in the pathogenesis of RIF.

SUBMITTER: Wang H

PROVIDER: S-EPMC9427240 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Comprehensive Analysis of circRNA-Mediated ceRNA Regulatory Networks in relation to Recurrent Implantation Failure.

Wang Hanbing H Lv Wei W Zhu Yilin Y

Evidence-based complementary and alternative medicine : eCAM 20220823

Recurrent implantation failure (RIF) is attributed to endometrial receptivity dysfunction with many unanswered questions. Up to now, there is no explanation for RIF, and therapeutic strategies are usually limited to supportive care. In this study, we differentially analyzed the raw data deposited in three eligible microarray datasets, GSE111974, GSE121219, and GSE147442 to screen DE-mRNAs, DE-miRNAs, and DE-circRNAs, respectively. The value of log2-fold change |log2FC| ≥ 1 and the adjusted <i>p< ...[more]

PMID: 36051495

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Project description:RNAs are closely associated with human diseases; however, immune-related genes (IRGs) and their potential regulatory networks in relation to spinal cord injury (SCI) are still poorly understood. Here, we investigated the key IRGs as well as the competing endogenous RNA (ceRNA) mechanisms that are associated with SCI pathogenesis based on microarray datasets and the use of a rat SCI model. Specifically, four independent SCI microarray datasets from Gene Expression Omnibus (GEO) database were analyzed and, thereafter, differentially expressed IRGs were annotated via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Furthermore, based on the GEO datasets, differentially expressed RNAs (DERNAs), including DEcircRNAs, DEmiRNAs, and DEmRNAs were identified and interactions between them were also predicted using online databases, and to construct a circular RNA (circRNA) mediated ceRNA network, candidate RNAs were also identified. Furthermore, the support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) methods were used for the identification of critical DERNAs, while differential gene expression was validated using the GSE20907 dataset. Our results were as follows. In the SCI microarray datasets, 32, 58, and 74 DEIRGs, DEcircRNAs, and DEmiRNAs were identified, respectively. In addition, GO and KEGG analyses showed that the DEIRGs were primarily enriched in neutrophil-mediated immunity and nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor-1 (HIF-1) signaling pathways, and based on LASSO and SVM screening, PLXNB2 was identified as a DEIRG, while hsa_circ_0026646 was identified as the key circRNA, showing a higher SCI expression. Furthermore, our results proved that PLXNB2 and hsa_circ_0026646 were upregulated in SCI, whereas miR-331-3p was downregulated, and, interestingly, similar expression profiles were confirmed using the rat SCI model. Furthermore, fluorescent reporter assay indicated that both hsa_circ_0026646 and PLXNB2 have miR-331-3p target sites, and the ceRNA hypothesis suggested the dysregulation of hsa_circ_0026646, miR-331-3p, and PLXNB2 in SCI. Thus, our results suggested that in SCI pathogenesis, hsa_circ_0026646 correlates with PLXNB2 by targeting miR-331-3p.

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.

Project description:ObjectiveThe incidence of papillary thyroid cancer (PTC) concomitant with Hashimoto's thyroiditis (HT) is gradually increasing over the past decades. This study aims to identify differentially expressed lncRNAs between tumor tissues of PTC with or without HT and further to confer a better understanding of lncRNA-based competing endogenous RNA (ceRNA) network in PTC with HT.MethodsGSE138198 containing tissue mRNA data and GSE192560 containing lncRNA data were utilized to perform differentially expression analysis. The ceRNA network was constructed based on miRNA-mRNA interactions merging with lncRNA-microRNA interactions. Functional enrichment analysis and protein-protein interaction (PPI) analysis were performed. The mRNA levels of core genes in the PPI analysis in tumor tissues collected from 112 PTC patients including 35 cases coexistent with HT were determined by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsA total of 57 genes and 40 lncRNAs, with value of |log2 fold change (FC)|≥ 1 and the adjusted P-value < 0.05, were deemed as differentially expressed genes and lncRNAs between PTC with and without HT. The pathways most significantly enriched by differentially expressed genes between PTC with and without HT were viral protein interaction with cytokine and cytokine receptor and cytokine-cytokine receptor interaction. CXCL10, CXCL9, CCL5, FCGR3A, and CCR2 owned degree values not less than 10 were deemed as core genes differentially expressed between PTC with and without HT. A total of 76 pairs of lncRNA-miRNA-mRNA ceRNA were obtained. Results of qRT-PCR partially demonstrated the bioinformatics results that the mRNA levels of CXCL10, CXCL9, CCL5, and CCR2 were remarkably elevated in tumor tissues collected from PTC patients coexistent with HT than those without HT (P < 0.001).ConclusionOur study offers a better understanding of the lncRNA-related ceRNA network involved in PTC with HT, providing novel key genes associated with PTC coexistent with HT.

Dataset Information

Comprehensive Analysis of circRNA-Mediated ceRNA Regulatory Networks in relation to Recurrent Implantation Failure.

Publications

Comprehensive Analysis of circRNA-Mediated ceRNA Regulatory Networks in relation to Recurrent Implantation Failure.

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