scholarly journals Integrated miRNA and mRNA Expression Profiles Reveal Differentially Expressed miR-222a as an Antiviral Factor Against Duck Hepatitis A Virus Type 1 Infection

Author(s):  
Nana Sui ◽  
Ruihua Zhang ◽  
Yue Jiang ◽  
Honglei Yu ◽  
Guige Xu ◽  
...  

Duck hepatitis A virus 1 (DHAV-1) is a highly contagious etiological agent that causes acute hepatitis in young ducklings. MicroRNAs (miRNAs) play important regulatory roles in response to pathogens. However, the interplay between DHAV-1 infection and miRNAs remains ambiguous. We characterized and compared miRNA and mRNA expression profiles in duck embryo fibroblasts cells (DEFs) infected with DHAV-1. In total, 36 and 96 differentially expressed (DE) miRNAs, and 4110 and 2595 DE mRNAs, were identified at 12 and 24 h after infection. In particular, 126 and 275 miRNA–mRNA pairs with a negative correlation were chosen to construct an interaction network. Subsequently, we identified the functional annotation of DE mRNAs and target genes of DE miRNAs enriched in diverse Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which may be important for virus resistance, cell proliferation, and metabolism. Moreover, upregulated miR-222a could negatively regulate DHAV-1 replication in DEFs and downregulate integrin subunit beta 3 (ITGB3) expression by targeting the 3′ untranslated region (3′UTR), indicating that miR-222a may modulate DHAV-1 replication via interaction with ITGB3. In conclusion, the results reveal changes of mRNAs and miRNAs during DHAV-1 infection and suggest miR-222a as an antiviral factor against DHAV-1.

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9280
Author(s):  
Jijun Song ◽  
Mingxin Song

Background Echinococcosis caused by larval of Echinococcus is prevalent all over the world. Although clinical experience showed that the presence of tapeworms could not be found in liver lesions, the repeated infection and aggravation of lesions still occur in the host. Here, this study constructed a multifactor-driven disease-related dysfunction network to explore the potential molecular pathogenesis mechanism in different hosts after E.multilocularis infection. Method First, iTRAQ sequencing was performed on human liver infected with E.multilocularis. Second, obtained microRNAs(miRNAs) expression profiles of humans and canine infected with Echinococcus from the GEO database. In addition, we also performed differential expression analysis, protein interaction network analysis, enrichment analysis, and crosstalk analysis to obtain genes and modules related to E.multilocularis infection. Pivot analysis is used to calculate the potential regulatory effects of multiple factors on the module and identify related non-coding RNAs(ncRNAs) and transcription factors(TFs). Finally, we screened the target genes of miRNAs of Echinococcus to further explore its infection mechanism. Results A total of 267 differentially expressed proteins from humans and 3,635 differentially expressed genes from canine were obtained. They participated in 16 human-related dysfunction modules and five canine-related dysfunction modules, respectively. Both human and canine dysfunction modules are significantly involved in BMP signaling pathway and TGF-beta signaling pathway. In addition, pivot analysis found that 1,129 ncRNAs and 110 TFs significantly regulated human dysfunction modules, 158 ncRNAs and nine TFs significantly regulated canine dysfunction modules. Surprisingly, the Echinococcus miR-184 plays a role in the pathogenicity regulation by targeting nine TFs and one ncRNA in humans. Similarly, miR-184 can also cause physiological dysfunction by regulating two transcription factors in canine. Conclusion The results show that the miRNA-184 of Echinococcus can regulate the pathogenic process through various biological functions and pathways. The results laid a solid theoretical foundation for biologists to further explore the pathogenic mechanism of Echinococcosis.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhi Lv ◽  
Liping Sun ◽  
Qian Xu ◽  
Chengzhong Xing ◽  
Yuan Yuan

Abstract Background N6-methyladenosine (m6A) modification might be closely associated with the genesis and development of gastric cancer (GC). Currently, the evidence established by high-throughput assay for GC-related m6A patterns based on long non-coding RNAs (lncRNAs) remains limited. Here, a joint analysis of lncRNA m6A methylome and lncRNA/mRNA expression profiles in GC was performed to explore the regulatory roles of m6A modification in lncRNAs. Methods Three subjects with primary GC were enrolled in our study and paired sample was randomly selected from GC tissue and adjacent normal tissue for each case. Methylated RNA Immunoprecipitation NextGeneration Sequencing (MeRIP-Seq) and Microarray Gene Expression Profiling was subsequently performed. Then co-expression analysis and gene enrichment analysis were successively conducted. Results After data analysis, we identified 191 differentially m6A-methylated lncRNAs, 240 differentially expressed lncRNAs and 229 differentially expressed mRNAs in GC. Furthermore, four differentially m6A-methylated and expressed lncRNAs (dme-lncRNAs) were discovered including RASAL2-AS1, LINC00910, SNHG7 and LINC01105. Their potential target genes were explored by co-expression analysis. And gene enrichment analysis suggested that they might influence the cellular processes and biological behaviors involved in mitosis and cell cycle. The potential impacts of these targets on GC cells were further validated by CCLE database and literature review. Conclusions Four novel dme-lncRNAs were identified in GC, which might exert regulatory roles on GC cell proliferation. The present study would provide clues for the lncRNA m6A methylation-based research on GC epigenetic etiology and pathogenesis.


2019 ◽  
Vol 124 ◽  
pp. 256-262 ◽  
Author(s):  
Xuelian Zhang ◽  
Wenjing Zhang ◽  
Yue Liu ◽  
Haihui Qi ◽  
Chunxue Hao ◽  
...  

2021 ◽  
Author(s):  
Sangyeob Lee ◽  
Jun-Il Yoo

Abstract Background: Sarcopenia is an age-related disease with skeletal muscle loss, weakness, and functional impairment. The potential causes of sarcopenia including the programmed cell death of muscles, inflammation, reactive oxygen species, protein turnover, and mitochondrial dysfunction have been studied. The purpose of this study was to find differentially expressed miRNAs (DE-miRNAs) in the muscle samples of older people (GSE23527). In addition, we performed to identify new miRNA-mRNA regulatory network for treating sarcopeniaMethods: Gene expression profiles were obtained from microarray datasets (GSE8479 and GSE1428) of the vastus lateralis muscles of young and older male subjects. Dataset GSE23527 was derived from the platform of GPL10358 (LC_MRA-1001_miRHuman_11.0_080411) and contained microRNA arrays of 12 young muscle samples and 12 older muscle samples. The DEGs between the older and young GSE8479 and GSE1428 samples were identified using the online analysis tool imaGEO (https://imageo.genyo.es). Pathway and process enrichment analysis with the ontology sources in the KEGG pathway, GO biological processes, Reactome gene sets, WikiPathways, and CORUM were analyzed by Metascape. A PPI (protein-protein interaction) network of DEGs was constructed using the Search Tool for Retrieval of Interacting Genes (STRING) app in Cytoscape software (version 1.6.0). GEO2R (https://www.ncbi.nlm.nih.gov) was used to select differentially expressed miRNAs (DE-miRNAs) in the GSE 23527 dataset.Results: In the GSE8479 and GSE1428 datasets, a total of 81 DEGs were discovered, including four upregulated genes and 77 downregulated genes. The top 12 clusters and their representative enriched terms were identified using Metascape. A total of 79 nodes and 186 edges were predicted in the PPI network. One upregulated DE-miRNA (hsa-miR-450a-5p) and six downregulated DE-miRNAs (hsa-miR-127-3p, hsa-miR-24-2-5p, hsa-miR-378a-5p, hsa-miR-532-5p, hsa-miR-487b-5p, and has-miR-487b-3p) were selected in the miRBase database. The MiRWalk online database was utilized for exploring 8017 genes that were selected as genes regulated by DE-miRNAs and six of them overlapped with hub genes. COX7A1 and NDUFB5 showed significantly low expression in sarcopenia patients compared to the controls. COX7B and PDHA1 also displayed low expression in sarcopenia patients, but expression of COX7A1 and NDUFB5 was not significant. TIMM8A and CS showed similar expression rates in both samples.Conclusions: The present bioinformatics analysis showed that two target genes (COX7A1 and NDUFB5) were potentially downregulated in sarcopenia patients. These two genes could be the cause of sarcopenia with aging. In addition, present study showed that several miRNAs (hsa-miR-378a-5p, hsa-miR-532-5p, hsa-miR-127-3p, and hsa-miR-24-2-5p) were identified as regulating the target genes. These results suggest that controlling the identified miRNAs could be a prospective strategy for treating sarcopenia by regulating the mRNA-miRNA network.


2020 ◽  
Author(s):  
Jiaoyan Tan ◽  
Yan Wu ◽  
Jianping Guo ◽  
Huimin Li ◽  
Lili Zhu ◽  
...  

Abstract Background : The brown planthopper (BPH, Nilaparvata lugens Stål) is a kind of phloem-feeding pest that adversely affects rice yield. Recently, the BPH-resistance gene, BPH6 , was cloned and applied in rice breeding to effectively control BPH. However, the molecular mechanisms underlying BPH6 are poorly understood. Results: Here, an integrated miRNA and mRNA expression profiling analysis was performed on BPH6 -transgenic (BPH6G) and Nipponbare (wild type, WT) plants after BPH infestation, and a total of 217 differentially expressed miRNAs (DEMs) and 7,874 differentially expressed mRNAs (DEGs) were identified. 29 miRNAs, including members of miR160, miR166 and miR169 family were opposite expressed during early or late feeding stages between the two varieties, whilst 9 miRNAs were specifically expressed in BPH6G plants, suggesting involvement of these miRNAs in BPH6 -mediated resistance to BPH. In the transcriptome analysis, 949 DEGs were opposite expressed during early or late feeding stages of the two genotypes, which were enriched in metabolic processes, cellular development, cell wall organization, cellular component movement and hormone transport, and certain primary and secondary metabolite synthesis. 24 genes were further selected as candidates for BPH resistance. Integrated analysis of the DEMs and DEGs showed that 34 miRNAs corresponding to 42 target genes were candidate miRNA-mRNA pairs for BPH resistance, 18 pairs were verified by qRT-PCR, and two pairs were confirmed by in vivo analysis. Conclusions: For the first time, we reported integrated small RNA and transcriptome sequencing to illustrate resistance mechanisms against BPH in rice. Our results provide a valuable resource to ascertain changes in BPH-induced miRNA and mRNA expression profiles and enable to comprehend plant-insect interactions and find a way for efficient insect control.


2019 ◽  
Vol 20 (5) ◽  
pp. 1041 ◽  
Author(s):  
Shuo Gao ◽  
Hao Jiang ◽  
Jie Sun ◽  
Youxiang Diao ◽  
Yi Tang ◽  
...  

The Reticuloendotheliosis virus (REV) primarily causes avian severe immunosuppression, in addition to other symptoms, which include avian dwarfing syndrome and chronic tumors in lymphoid and other tissue. To date, REV’s molecular mechanisms leading to immunosuppression have not been fully elucidated. In the current study, we aimed to elucidate the role of microRNAs (miRNA) in regulating gene expression during REV infections. Therefore, we used a high-dose spleen necrosis virus (SNV) model of REV to inoculate one-day-old specific pathogen-free (SPF) chickens, thereby inducing congenital infections. We analyzed miRNA and mRNA expression profiles using Next Generation Sequencing (NGS) in a total of 19 spleen samples that were collected at 7, 14, and 21 days post infection (dpi). The results showed that 63 differentially expressed miRNAs (DEmiRNAs) (30 known miRNAs and 33 novel miRNAs) and 482 differentially expressed target genes (DETGs) were identified. Integration analysis identified 886 known miRNA–mRNA and 580 novel miRNA–mRNA interaction pairs, which involved miRNAs that were inversely correlated with the above DETGs. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DETGs were considerably enriched in the immune-relevant pathways category, such as immune system, cell growth and death, signaling molecules and interaction, signal transduction, etc. We further verified selected immune-relevant miRNA and their DETGs while using quantitative RT-PCR (qRT-PCR). Overall, our data revealed valuable immune-related miRNA–mRNA interaction information that occurred during REV infections, thereby broadening our understanding of the REV-induced immunosuppression.


Lupus ◽  
2020 ◽  
Vol 29 (8) ◽  
pp. 854-861
Author(s):  
Jianbo Song ◽  
Liqin Zhao ◽  
Yuanping Li

Objective Lupus nephritis (LN) is one of the serious complications of systemic lupus erythematosus. The aim of this study was to identify core genes and pathways involved in the pathogenesis of LN. Methods We screened differentially expressed genes (DEGs) in LN patients using mRNA expression profile data from the Gene Expression Omnibus. The functional and pathway enrichment analysis of DEGs was performed utilizing the Database for annotation, Visualization and Integrated Discovery. Target genes with differentially expressed miRNAs (DEMIs) were predicted using the miRTarBase database, and the intersection between these target genes and DEGs was selected to be studied further. Results In total, 107 common DEGs (CDEGs) were identified from the Tub_LN group and Glom_LN group, and 66 DEMIs were identified. Fifty-three hub genes and two significant modules were identified from the protein–protein interaction (PPI) network, and a miRNA–mRNA network was constructed. The CDEGs, module genes in the PPI network and genes intersecting with the CDEGs and target genes of DEMIs were all associated with the PI3K-Akt signalling pathway. Conclusion In summary, this study reveals some crucial genes and pathways potentially involving in the pathogenesis of LN. These findings provide a new insight for the research and treatment of LN.


2019 ◽  
Author(s):  
Jiaoyan Tan ◽  
Yan Wu ◽  
Jianping Guo ◽  
Huimin Li ◽  
Lili Zhu ◽  
...  

Abstract Background: The brown planthopper (BPH, Nilaparvata lugens Stål) is a kind of phloem-feeding pest that adversely affects rice yield. Recently, the BPH-resistance gene, BPH6, was cloned and applied in rice breeding to effectively control BPH. However, the molecular mechanisms underlying BPH6 are poorly understood. Results: Here, an integrated miRNA and mRNA expression profiling analysis was performed on BPH6-transgenic (BPH6G) and Nipponbare (wild type, WT) plants after BPH infestation, and a total of 217 differentially expressed miRNAs (DEMs) and 7,874 differentially expressed mRNAs (DEGs) were identified. 29 miRNAs, including members of miR160, miR166 and miR169 family were opposite expressed during early or late feeding stages between the two varieties, whilst 9 miRNAs were specifically expressed in BPH6G plants, suggesting involvement of these miRNAs in BPH6-mediated resistance to BPH. In the transcriptome analysis, 949 DEGs were opposite expressed during early or late feeding stages of the two genotypes, which were enriched in metabolic processes, cellular development, cell wall organization, cellular component movement and hormone transport, and certain primary and secondary metabolite synthesis. 24 genes were further selected as candidates for BPH resistance. Integrated analysis of the DEMs and DEGs showed that 34 miRNAs corresponding to 42 target genes were candidate miRNA-mRNA pairs for BPH resistance, 18 pairs were verified by qRT-PCR, and two pairs were confirmed by in vivo analysis. Conclusions: For the first time, we reported integrated small RNA and transcriptome sequencing to illustrate resistance mechanisms against BPH in rice. Our results provide a valuable resource to ascertain changes in BPH-induced miRNA and mRNA expression profiles and enables the analysis of the comprehensive plant-insect interactions required for efficient insect control.


2020 ◽  
Vol 15 ◽  
Author(s):  
Yeqing Sun ◽  
Lei Chen ◽  
Yingqi Zhang ◽  
Jincheng Zhang ◽  
Shashi Ranjan Tiwari

Background: Osteoarthritis (OA), one of the most important causes leading to joint disability, was considered as an untreatable disease. A series of genes were reported to regulate the pathogenesis of OA, including microRNAs, Long non-coding RNAs and Circular RNA. So far, the expression profiles and functions of lncRNAs, mRNAs, and circRNAs in OA are not fully understood. Objective: The present study aimed to identify differently expressed genes in OA. Methods: The present study conducted RNA-seq to identify differently expressed genes in OA. Ontology (GO) analysis was used to analysis the Molecular Function and Biological Process. KEGG pathway analysis was used to perform the differentially expressed lncRNAs in biological pathways. Results: Hierarchical clustering revealed a total of 943 mRNAs, 518 lncRNAs, and 300 circRNAs were dysregulated in OA compared to normal samples. Furthermore, we constructed differentially expressed mRNAs mediated proteinprotein interaction network, differentially expressed lncRNAs mediated trans regulatory networks, and competitive endogenous RNA (ceRNA) to reveal the interaction among these genes in OA. Bioinformatics analysis revealed these dysregulated genes were involved in regulating multiple biological processes, such as wound healing, negative regulation of ossification, sister chromatid cohesion, positive regulation of interleukin-1 alpha production, sodium ion transmembrane transport, positive regulation of cell migration, and negative regulation of inflammatory response. To the best of our knowledge, this study for the first time revealed the expression pattern of mRNAs, lncRNAs and circRNAs in OA. Conclusion: This study provided novel information to validate these differentially expressed RNAs may be as possible biomarkers and targets in OA.


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