Identification of Immune-Related lncRNA Regulatory Network in Pulpitis.
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ABSTRACT: Background
Long noncoding RNAs (lncRNAs) are emerging as critical regulators of various biological processes, including immune regulation.Methods
Due to the critical significance of immunological responses in the development and progression of pulpitis, we used an integrated algorithm to identify immune-related lncRNAs and then examined the lncRNA-immunity regulation network in pulpitis. Before identifying immune-related lncRNAs, the data from GEO datasets were precleaned. ConsensusClusterPlus was used to differentiate immune-related pulpitis subgroups. Enrichment analysis using GO and MSigDB databases was employed to determine the differences in molecular function, cellular component, and biological process between the two pulpitis subtypes.Results
An integrated algorithm was designed to filtrate immune-related lncRNAs accurately. 790 immune-related lncRNAs were found in 17 immunological categories, with 38 of them perturbated in pulpitis. The Cytoscape software was used to visualize the relationship between representative immune regulatory pathways and immune-related lncRNAs. Two immune-related pulpitis subtypes were discovered using differentially expressed immune-related lncRNAs. Subtype 2 has a stronger association with immune-related pathways than subtype 1 does.Conclusions
Our study identified many immune-related lncRNAs and investigated potential lncRNA regulation networks; meanwhile, the molecular subtypes of pulpitis were identified, all of which will be relevant for further research into inflammatory and immunological processes in pulpitis.
SUBMITTER: Du J
PROVIDER: S-EPMC9194960 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Identification of Immune-Related lncRNA Regulatory Network in Pulpitis.
Du Jing J Liu Liu L Yang Fan F Yang Fan F Leng Sha S Zhang Lan L Huang Dingming D
Disease markers 20220606
<h4>Background</h4>Long noncoding RNAs (lncRNAs) are emerging as critical regulators of various biological processes, including immune regulation.<h4>Methods</h4>Due to the critical significance of immunological responses in the development and progression of pulpitis, we used an integrated algorithm to identify immune-related lncRNAs and then examined the lncRNA-immunity regulation network in pulpitis. Before identifying immune-related lncRNAs, the data from GEO datasets were precleaned. Consen ...[more]
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Project description:BackgroundSepsis is a high mortality disease which seriously threatens human life and health, for which the pathogenetic mechanism still unclear. There is increasing evidence showed that immune and inflammation responses are key players in the development of sepsis pathology. LncRNAs, which act as ceRNAs, have critical roles in various diseases. However, the regulatory roles of ceRNA in the immunopathogenesis of sepsis have not yet been elucidated.ResultsIn this study, we aimed to identify immune biomarkers associated with sepsis. We first generated a global immune-associated ceRNA (IMCE) network based on data describing interactions pairs of gene-miRNA and miRNA-lncRNA. Afterward, we excavated a dysregulated sepsis immune-associated ceRNA (SPIMC) network from the global IMCE network by means of a multi-step computational approach. Functional enrichment indicated that lncRNAs in SPIMC network have pivotal roles in the immune mechanism underlying sepsis. Subsequently, we identified module and hub genes (CD4 and STAT4) via construction of a sepsis immune-related PPI network. Then, we identified hub genes based on the modular structure of PPI network and generated a ceRNA subnetwork to analyze key lncRNAs associated with sepsis. Finally, 6 lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) that identified as immune biomarkers of sepsis. Moreover, the CIBERSORT algorithm and the infiltration of circulating immune cells types were performed to identify the inflammatory state of sepsis. Correlation analyses between immune cells and sepsis immune biomarkers showed that the LINC00265 was strongly positive correlated with the macrophages M2 (r = 0.77).ConclusionCollectively, these results may suggest that these lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) played important roles in the immune pathogenesis of sepsis and provide potential therapeutic targets for further researches on immune therapy treatment in patients with sepsis.
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Project description:Long non-coding RNAs (lncRNAs) are ncRNA transcripts >200 nucleotides that are important genetic regulators. LncRNAs can directly regulate mRNA through a lncRNA-mRNA regulatory mode and can also regulate mRNA through competitive binding to micro (mi)RNA, which is generally known as the competitive endogenous RNA (ceRNA) network. The present study evaluated the functional roles and regulatory networks of lncRNAs in chronic glomerulonephritis (CGN). The proliferative ability of mouse glomerular mesangial cells (GMCs) induced by different concentrations of lipopolysaccharide (LPS) was assessed using the Cell Counting Kit-8 assay, and RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs in LPS-induced GMCs. Based on the sequencing results, six lncRNAs were selected for validation using reverse transcription-quantitative PCR (RT-qPCR). Furthermore, the lncRNA-mRNA regulatory network and the lncRNA-miRNA-mRNA ceRNA network were constructed to assess the role and mechanism of CGN-related lncRNAs. To elucidate the biological functions of lncRNAs, Gene Ontology (GO) biological process term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on all mRNAs involved in the lncRNA-mRNA regulatory network and in the ceRNA network. A total of 1,532 differentially expressed lncRNAs, including 594 upregulated lncRNAs and 938 downregulated lncRNAs, were identified using RNA-seq. The results of RT-qPCR validation were consistent with RNA-seq results. An lncRNA-mRNA regulatory network, including 236 lncRNAs and 556 mRNAs, and a ceRNA network, including 6 lncRNAs, 18 miRNAs and 419 mRNAs, were successfully constructed. The GO biological process term enrichment and KEGG pathway enrichment analyses demonstrated that those lncRNAs were often related to inflammatory response and substance metabolism. The present study identified key CGN-related lncRNAs in LPS-induced GMCs, and further demonstrated a global view of the lncRNA-mRNA regulatory network and ceRNA network involved in CGN. These results offered novel insights into the roles of lncRNAs in the pathogenesis of CGN and identified potential diagnostic biomarkers.
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Project description:LncRNAs are regulatory noncoding RNAs that play crucial roles in many biological processes. The dysregulation of lncRNA is thought to be involved in many complex diseases; lncRNAs are often the targets of miRNAs in the indirect regulation of gene expression. Numerous studies have indicated that miRNA-lncRNA interactions are closely related to the occurrence and development of cancers. Thus, it is important to develop an effective method for the identification of cancer-related miRNA-lncRNA interactions. In this study, we compiled 155653 experimentally validated and predicted miRNA-lncRNA associations, which we defined as basic interactions. We next constructed an individual-specific miRNA-lncRNA network (ISMLN) for each cancer sample and a basic miRNA-lncRNA network (BMLN) for each type of cancer by examining the expression profiles of miRNAs and lncRNAs in the TCGA (The Cancer Genome Atlas) database. We then selected potential miRNA-lncRNA biomarkers based on the BLMN. Using this method, we identified cancer-related miRNA-lncRNA biomarkers and modules specific to a certain cancer. This method of profiling will contribute to the diagnosis and treatment of cancers at the level of gene regulatory networks.
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Project description:Inflammatory reaction of pulp tissue plays a role in the pathogen elimination and tissue repair. The evaluation of severity of pulpitis can serve an instructive function in therapeutic scheme. However, there are many limitations in the traditional evaluation methods for the severity of pulpitis. Based on the Gene Expression Omnibus (GEO) database, our study discovered 843 differentially expressed genes (DEGs) related to pulpitis. Afterwards, we constructed a protein-protein interaction (PPI) network of DEGs and used MCODE plugin to determine the key functional subset. Meanwhile, genes in the key functional subset were subjected to GO and KEGG enrichment analyses. The result showed that genes were mainly enriched in inflammatory reaction-related functions. Next, we screened out intersections of PPI network nodes and pulpitis-related genes. Then, 20 genes were obtained as seed genes. In the PPI network, 50 genes that had the highest correlation with seed genes were screened out using random walk with restart (RWR). Furthermore, 4 pulpitis-related hub genes were obtained from the intersection of the top 50 genes and genes in the key functional subset. Finally, GeneMANIA was utilized to predict genes coexpressed with hub genes, and expression levels of the 4 hub genes in normal and pulpitis groups were analyzed based on GEO data. The result demonstrated that the 4 hub genes were mainly coexpressed with chemokine-related genes and were remarkably upregulated in the pulpitis group. In short, we eventually determined 4 potential biomarkers of pulpitis.
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Project description:BackgroundLong noncoding RNAs (lncRNAs) play important roles in the regulation of immunological and apoptotic function. This study aimed to explore the critical immune- and apoptosis-related lncRNAs in the occurrence and development of Henoch-Schönlein purpura nephritis (HSPN) in children.MethodsDifferential analysis was employed to identify the differentially expressed lncRNAs, as well as the immune- and apoptosis-related mRNAs in children with HSPN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to validate the immunological and apoptotic roles of the differentially expressed immune- and apoptosis-related lncRNAs and mRNAs. Spearman's correlation analysis was performed to analyze the differentially expressed lncRNAs and immune- and apoptosis-related messenger RNAs (mRNAs). Based on the competing endogenous RNA (ceRNA) mechanism, the immune- and apoptosis-related lncRNA-microRNA (miRNA)-mRNA regulatory network was then constructed in children with HSPN. The expression levels of the lncRNAs in the lncRNA-miRNA-mRNA regulatory network were further confirmed by quantitative real-time polymerase chain in the peripheral blood samples of children with HSPN.ResultsBy intersecting the differentially expressed immune-related and apoptosis-related genes through GO and KEGG analyses, a total of 43 genes were identified in children with HSPN, and 100 lncRNAs highly correlated with the above genes were identified by correlation analysis. The immune- and apoptosis-related lncRNA-miRNA-mRNA regulatory network was then established based on ceRNA mechanism. Dysregulation of a total of 11 lncRNAs were discovered, including upregulated SNHG3, LINC00152, TUG1, GAS5, FGD5-AS1, DLEU2, and SCARNA9; and downregulated SNHG1, NEAT1, DISC1-IT1, and PVT1. The validation conducted in the clinical samples also suggested that the above lncRNAs in the specific regulatory network may act as potential biomarkers with prognosis in children with HSPN.ConclusionsLncRNAs may play essential regulatory roles in the occurrence and development of HSPN in children, and the immune- and apoptosis-related lncRNA-miRNA-mRNA regulatory network might be the underlying molecular mechanism that dissects the disease pathogenesis. In addition, the dysregulated lncRNAs in the regulatory network may be novel biomarkers for the diagnosis and therapy of HSPN in children.
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