Comprehensive analyses of function and molecular interaction of differentially expressed non-coding RNAs and mRNA in Hantaan virus infection
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ABSTRACT: Hantaan virus (HTNV), the prevalent prototype of the hantavirus in Asia, causes hemorrhagic fever with renal syndrome (HFRS) with high mortality in human being. However, the pathogenesis of HTNV infection remains elusive. Accumulating evidences indicate that non-coding RNAs (ncRNAs), including long non-coding RNA (lncRNA), circular RNA (circRNA) and microRNA (miRNA) play crucial roles in the progression of virus infection. Here, we identified differential lncRNA/miRNA/circRNA and mRNA expression profiles of HTNV-infected human umbilical vein endothelial cells (HUVECs) compared with mock-infected HUVECs by whole transcriptome sequencing. Subsequently, comprehensive bioinformatics analyses established miRNA-mRNA co-expression, protein-protein interaction and competing endogenous RNA (ceRNA) networks in miRNA-lncRNA-circRNA-mRNA regulatory axis. The trans or cis regulatory roles of identified RNAs on HTNV infection were ascertained by RNA interference and key ceRNA relationships were verified by dual-luciferase reporter experiments. Moreover, gene ontology (GO) enrichment analysis showed that dysregulated RNAs were mostly related to antiviral innate immune response. In conclusion, our findings firstly revealed that circRNAs and ceRNA network were involved in regulating HTNV infection, and also confirmed several key lncRNAs and miRNAs which had vital effects on HTNV infection. The identification and characterization of RNAs provide the new insights on ceRNA networks in HTNV-host interactions, which lays the foundation for future research of the potential roles of ncRNAs in the pathogenesis of HFRS.
Project description:Hantaan virus (HTNV), the prevalent prototype of the hantavirus in Asia, causes hemorrhagic fever with renal syndrome (HFRS) with high mortality in human being. However, the pathogenesis of HTNV infection remains elusive. Accumulating evidences indicate that non-coding RNAs (ncRNAs), including long non-coding RNA (lncRNA), circular RNA (circRNA) and microRNA (miRNA) play crucial roles in the progression of virus infection. Here, we identified differential lncRNA/miRNA/circRNA and mRNA expression profiles of HTNV-infected human umbilical vein endothelial cells (HUVECs) compared with mock-infected HUVECs by whole transcriptome sequencing. Subsequently, comprehensive bioinformatics analyses established miRNA-mRNA co-expression, protein-protein interaction and competing endogenous RNA (ceRNA) networks in miRNA-lncRNA-circRNA-mRNA regulatory axis. The trans or cis regulatory roles of identified RNAs on HTNV infection were ascertained by RNA interference and key ceRNA relationships were verified by dual-luciferase reporter experiments. Moreover, gene ontology (GO) enrichment analysis showed that dysregulated RNAs were mostly related to antiviral innate immune response. In conclusion, our findings firstly revealed that circRNAs and ceRNA network were involved in regulating HTNV infection, and also confirmed several key lncRNAs and miRNAs which had vital effects on HTNV infection. The identification and characterization of RNAs provide the new insights on ceRNA networks in HTNV-host interactions, which lays the foundation for future research of the potential roles of ncRNAs in the pathogenesis of HFRS.
Project description:Hantaan virus (HTNV), the prevalent prototype of the hantavirus in Asia, causes hemorrhagic fever with renal syndrome (HFRS) with high mortality in human being. However, the pathogenesis of HTNV infection remains elusive. Accumulating evidences indicate that non-coding RNAs (ncRNAs), including long non-coding RNA (lncRNA), circular RNA (circRNA) and microRNA (miRNA) play crucial roles in the progression of virus infection. Here, we identified differential lncRNA/miRNA/circRNA and mRNA expression profiles of HTNV-infected human umbilical vein endothelial cells (HUVECs) compared with mock-infected HUVECs by whole transcriptome sequencing. Subsequently, comprehensive bioinformatics analyses established miRNA-mRNA co-expression, protein-protein interaction and competing endogenous RNA (ceRNA) networks in miRNA-lncRNA-circRNA-mRNA regulatory axis. The trans or cis regulatory roles of identified RNAs on HTNV infection were ascertained by RNA interference and key ceRNA relationships were verified by dual-luciferase reporter experiments. Moreover, gene ontology (GO) enrichment analysis showed that dysregulated RNAs were mostly related to antiviral innate immune response. In conclusion, our findings firstly revealed that circRNAs and ceRNA network were involved in regulating HTNV infection, and also confirmed several key lncRNAs and miRNAs which had vital effects on HTNV infection. The identification and characterization of RNAs provide the new insights on ceRNA networks in HTNV-host interactions, which lays the foundation for future research of the potential roles of ncRNAs in the pathogenesis of HFRS.
Project description:Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon stimulate genes (ISGs) play important roles in viral infection. However, the role of ISGs in HTNV infection is unclear. In this study, we observed the alteration of gene expression in HUVECs infected with HTNV compared with mock infected control and found considerable changes in mRNA and lncRNA profiles.
Project description:Lupus nephritis (LN) is a well-known complication of SLE, which is the leading cause of morbidity and mortality. mRNA and non-coding RNAs, including long non-coding RNA (lncRNA), circular RNA (circRNA) and microRNA(miRNA), could play important roles in LN onset and development. In this study, we identified differential lncRNA/miRNA/circRNA and mRNA expression profiles of renal tissues from LN patients compared with the healthy renal tissues by whole transcriptome sequencing. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the potential functions of these DE mRNAs and ncRNAs. Besides, the competing endogenous RNA (ceRNA) networks (circRNA-miRNA-mRNA network) were also constructed to understand the internal regulating relationships of these mRNAs and circRNAs. And key ceRNA relationships were verified by dual-luciferase reporter experiments. Moreover, gene function enrichment analysis showed that dysregulated RNAs were mostly related to innate and adaptive immune response, especially against virus infection. The analysis for these DE mRNAs and ncRNAs in LN patients provided a new perspective for the pathophysiology, diagnosis, and treatment of LN.
Project description:The purpose of this study is to identify dysregulated ncRNAs and understand how they influence Rotator cuff tears (RCT). We performed RNA sequencing and miRNA sequencing on 5 pairs of torn supraspinatus muscles and matched unharmed subscapularis muscles to identify RNAs dysregulated in RCT patients. Based on the results of differential expression analysis and miRNA targeting information, we constructed lncRNA/circRNA-associated dysregulated ceRNA networks in RCT. We found the largest module in the ceRNA network and identified several important ncRNAs in this module, which may have critical roles in RCT.
Project description:The purpose of this study is to identify dysregulated ncRNAs and understand how they influence Rotator cuff tears (RCT). We performed RNA sequencing and miRNA sequencing on 5 pairs of torn supraspinatus muscles and matched unharmed subscapularis muscles to identify RNAs dysregulated in RCT patients. Based on the results of differential expression analysis and miRNA targeting information, we constructed lncRNA/circRNA-associated dysregulated ceRNA networks in RCT. We found the largest module in the ceRNA network and identified several important ncRNAs in this module, which may have critical roles in RCT.
Project description:Hemorrhagic Fever with Renal Syndrome (HFRS) is a regional infectious disease of epidemic potential caused by the Hantaan Virus (HTNV).The studies on immunological responses during HTNV infection have continuously been performed. During HTNV infection, lymphocytes are following a tightly controlled genetic programme.The pathological changes of PBMCs also occured during HTNV infection. We used single cell RNA sequencing to detail the cellular components and gene expression profiles of PBMCs underlying HTNV infection.
Project description:Smal RNA is a type of single-stranded small-molecule RNA with a size of about 18-40 bases, mainly including microRNA, piRNA, snoRNA, snRNA, tRNA and so on. Small RNAs have important regulatory functions in cells and have the potential to be used as disease diagnostic markers or drug targets. We report the results of all small RNAs in exosomes from HTNV infected/uninfected HUVECs by high-throughput sequencing technology. We find that the transcriptomes of Exo-NC group (exosomes from HTNV uninfected cells) and Exo-HV group (exosomes from HTNV infected cells) expressed distinctly different expression patterns of miRNA.
Project description:Interventions: Gold Standard:Colonoscopy and tissue case biopsy;Index test:EVs nucleic acid combination (miRNA, lncRNA, circRNA) detection system.
Primary outcome(s): RNA;SEN, SPE, ACC, AUC of ROC
Study Design: Factorial
Project description:Hemorrhagic fever with renal syndrome (HFRS) caused by hantaan virus (HTNV) infection displays variable clinical signs. Humoral responses are important players against HTNV infections, however, this process is poorly understood. Herein, we investigated the phenotype, temporal dynamics, and characteristics of B-cell receptor repertoire (BCR) in a patient cohort with HFRS. The serological profile was characterized by low expression level of NP-specific antibody in severe cases. Importantly, B-cell subsets were activated and proliferated within the first two weeks of symptom onset, and the moderate cases reacted more rapidly. BCR analysis in the recovery phase revealed immunoglobulin gene diversity had dramatical rise and progressed more significant in the moderate group. The transcription of gene sets related to B-cell was lower, but the inflammatory sets were over-activated in severe cases. These data suggested the clinical signs and diseases recovery in HFRS patients were benefitted from rapid and efficacious humoral responses.