scholarly journals Identification of differentially expressed circulating exosomal lncRNAs in IgA nephropathy patients

2020 ◽  
Author(s):  
Qiongqiong Yang ◽  
Na Guo ◽  
Qin Zhou ◽  
Xiang Huang ◽  
Jianwen Yu ◽  
...  

Abstract Background: Immunoglobulin A nephropathy (IgAN) is one of the most prevalent primary glomerular disease. Non-invasive biomarkers are urgently needed for IgAN diagnosis. We investigate the difference in expression profiles of exosomal long non-coding-RNAs (lncRNAs) in plasma from IgAN patients compared with their healthy first-degree relatives, which may reveal novel non-invasive IgAN biomarkers. Methods: Exosomes were isolated from the plasma of IgAN patients and their healthy first-degree relatives. High-throughput RNA sequencing and real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate lncRNA expression profiles. Pathway enrichment analysis was used to predict their nearest protein-coding genes. Results: lncRNA-G21551 was significantly down-regulated in IgAN patients. The nearest protein-coding gene was found to be encoding the low affinity receptor of the Fc segment of immunoglobulin G (FCGR3B). Conclusion: Exosomal lncRNA-G21551, with FCGR3B as the nearest protein-coding gene, was down-regulated in IgAN patients, indicating its potential to serve as a non-invasive biomarker for IgAN.

2020 ◽  
Author(s):  
Na Guo ◽  
Qin Zhou ◽  
Xiang Huang ◽  
Jianwen Yu ◽  
Qianqian Han ◽  
...  

Abstract Background: Immunoglobulin A nephropathy (IgAN) is one of the most prevalent primary glomerular disease. Non-invasive biomarkers are urgently needed for IgAN diagnosis. We investigate the difference in expression profiles of exosomal long non-coding-RNAs (lncRNAs) in plasma from IgAN patients compared with their healthy first-degree relatives, which may reveal novel non-invasive IgAN biomarkers. Methods: Exosomes were isolated from the plasma of IgAN patients and their healthy first-degree relatives. High-throughput RNA sequencing and real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate lncRNA expression profiles. Pathway enrichment analysis was used to predict their nearest protein-coding genes. Results: lncRNA-G21551 was significantly down-regulated in IgAN patients. The nearest protein-coding gene was found to be encoding the low affinity receptor of the Fc segment of immunoglobulin G (FCGR3B). Conclusion: Exosomal lncRNA-G21551, with FCGR3B as the nearest protein-coding gene, was down-regulated in IgAN patients, indicating its potential to serve as a non-invasive biomarker for IgAN.


2020 ◽  
Author(s):  
Na Guo ◽  
Qin Zhou ◽  
Xiang Huang ◽  
Jianwen Yu ◽  
Qianqian Han ◽  
...  

Abstract Background: Although immunoglobulin A nephropathy (IgAN) is one of the foremost primary glomerular disease, treatment of IgAN is still in infancy. Non-invasive biomarkers are urgently needed for IgAN diagnosis. We investigate the difference in expression profiles of exosomal long non-coding-RNAs (lncRNAs) in plasma from IgAN patients compared with their healthy first-degree relatives, which may reveal novel non-invasive IgAN biomarkers. Methods: We isolated exosomes from the plasma of both IgAN patients and their healthy first-degree relatives. High-throughput RNA sequencing and real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate lncRNA expression profiles. Pathway enrichment analysis was used to predict their nearest protein-coding genes. Results: lncRNA-G21551 was significantly down-regulated in IgAN patients. Interestingly, the nearest protein-coding gene of lncRNA-G21551 was found to be encoding the low affinity receptor of the Fc segment of immunoglobulin G (FCGR3B). Conclusions: Exosomal lncRNA-G21551, with FCGR3B as the nearest protein-coding gene, was down-regulated in IgAN patients, indicating its potential to serve as a non-invasive biomarker for IgAN. Background: Although Immunoglobulin A nephropathy (IgAN) is one of the foremost primary glomerular disease, treatment of IgAN is still in infancy. Non-invasive biomarkers are urgently needed for IgAN diagnosis. We investigate the difference in expression profiles of exosomal long non-coding-RNAs (lncRNAs) in plasma from IgAN patients compared with their healthy first-degree relatives, which may reveal novel non-invasive IgAN biomarkers. Methods: We isolated exosomes from the plasma of both IgAN patients and their healthy first-degree relatives. High-throughput RNA sequencing and real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate lncRNA expression profiles. Pathway enrichment analysis was used to predict their nearest protein-coding genes. Results: lncRNA-G21551 was significantly down-regulated in IgAN patients. Interestingly, the nearest protein-coding gene of lncRNA-G21551 was found to be encoding the low affinity receptor of the Fc segment of immunoglobulin G (FCGR3B). Conclusions: Exosomal lncRNA-G21551, with FCGR3B as the nearest protein-coding gene, was down-regulated in IgAN patients, indicating its potential to serve as a non-invasive biomarker for IgAN.


2021 ◽  
Author(s):  
Xiaojie Shi ◽  
Qi Zhang ◽  
Jingjing Wang ◽  
Yuting Zhang ◽  
Yuchao Yan ◽  
...  

Abstract Background: Long non-coding RNAs (LncRNAs) are transcripts longer than 200 nucleotides with no protein-coding ability and exert crucial effects on viral infection and host immune responses. Porcine Epidemic Diarrhea Virus (PEDV) is a coronavirus that seriously affects the swine industry. However, our understanding of the function of lncRNA involved in host-PEDV interaction is limited.Results: A total of 1197 mRNA transcripts, 539 lncRNA transcripts, and 208 miRNA transcripts were differentially regulated at 24 h and 48 h post-infection. Moreover, gene ontology (GO) and KEGG pathway enrichment analysis showed that DE mRNAs and DE lncRNAs were mainly involved in biosynthesis, innate immunity, and lipid metabolism. Ten differentially expressed genes were randomly selected and validated by reverse-transcription qRT-PCR. In addition, we constructed a miRNA-mRNA-pathway network followed by a lncRNA-miRNA-mRNA ceRNA network.Conclusions: The present study is the first to reveal the global expression profiles of mRNAs, lncRNAs, and miRNAs during PEDV infection. We comprehensively characterize the ceRNA networks which can provide new insights into the pathogenesis of PEDV.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suthanthiram Backiyarani ◽  
Rajendran Sasikala ◽  
Simeon Sharmiladevi ◽  
Subbaraya Uma

AbstractBanana, one of the most important staple fruit among global consumers is highly sterile owing to natural parthenocarpy. Identification of genetic factors responsible for parthenocarpy would facilitate the conventional breeders to improve the seeded accessions. We have constructed Protein–protein interaction (PPI) network through mining differentially expressed genes and the genes used for transgenic studies with respect to parthenocarpy. Based on the topological and pathway enrichment analysis of proteins in PPI network, 12 candidate genes were shortlisted. By further validating these candidate genes in seeded and seedless accession of Musa spp. we put forward MaAGL8, MaMADS16, MaGH3.8, MaMADS29, MaRGA1, MaEXPA1, MaGID1C, MaHK2 and MaBAM1 as possible target genes in the study of natural parthenocarpy. In contrary, expression profile of MaACLB-2 and MaZEP is anticipated to highlight the difference in artificially induced and natural parthenocarpy. By exploring the PPI of validated genes from the network, we postulated a putative pathway that bring insights into the significance of cytokinin mediated CLAVATA(CLV)–WUSHEL(WUS) signaling pathway in addition to gibberellin mediated auxin signaling in parthenocarpy. Our analysis is the first attempt to identify candidate genes and to hypothesize a putative mechanism that bridges the gaps in understanding natural parthenocarpy through PPI network.


2021 ◽  
Author(s):  
Li Guoquan ◽  
Du Junwei ◽  
He Qi ◽  
Fu Xinghao ◽  
Ji Feihong ◽  
...  

Abstract BackgroundHashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a common autoimmune disease, which mainly occurs in women. The early manifestation was hyperthyroidism, however, hypothyroidism may occur if HT was not controlled for a long time. Numerous studies have shown that multiple factors, including genetic, environmental, and autoimmune factors, were involved in the pathogenesis of the disease, but the exact mechanisms were not yet clear. The aim of this study was to identify differentially expressed genes (DEGs) by comprehensive analysis and to provide specific insights into HT. MethodsTwo gene expression profiles (GSE6339, GSE138198) about HT were downloaded from the Gene Expression Omnibus (GEO) database. The DEGs were assessed between the HT and normal groups using the GEO2R. The DEGs were then sent to the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub genes were discovered using Cytoscape and CytoHubba. Finally, NetworkAnalyst was utilized to create the hub genes' targeted microRNAs (miRNAs). ResultsA total of 62 DEGs were discovered, including 60 up-regulated and 2 down-regulated DEGs. The signaling pathways were mainly engaged in cytokine interaction and cytotoxicity, and the DEGs were mostly enriched in immunological and inflammatory responses. IL2RA, CXCL9, IL10RA, CCL3, CCL4, CCL2, STAT1, CD4, CSF1R, and ITGAX were chosen as hub genes based on the results of the protein-protein interaction (PPI) network and CytoHubba. Five miRNAs, including mir-24-3p, mir-223-3p, mir-155-5p, mir-34a-5p, mir-26b-5p, and mir-6499-3p, were suggested as likely important miRNAs in HT. ConclusionsThese hub genes, pathways and miRNAs contribute to a better understanding of the pathophysiology of HT and offer potential treatment options for HT.


2021 ◽  
Author(s):  
Perumal Jayaraj ◽  
Seema Sen ◽  
Pranjal Vats ◽  
Shefali Dahiya ◽  
Vanshika Mohindroo

Background: Eyelid BCC accounts for more than 90% of Eyelid malignant neoplasms. Various aberrant signalling pathways and genes in Non-Ocular BCC have been found whereas Eyelid bcc remains elusive. Objective: This study aims to find the common DEGs of Eyelid and Non-Ocular BCC using bioinformatic analysis and text mining to gain more insights into the molecular aspects common to both BCC non-ocular and Eyelid BCC and to identify common potential prognostic markers. Material and method: The Gene Expression profiles of Eyelid BCC (GSE103439) and Non-Ocular BCC (GSE53462) were obtained from the NCBI GEO database followed by identification of common DEGs. Protein-Protein interaction and Pathway Enrichment analysis of these screened genes was done using bioinformatic tools like STRING, Cytoscape and BiNGO, DAVID, KEGG respectively. Results: A total of 181 genes were found common in both datasets. A PPI network was formed for the screened genes and 20 HUB genes were sorted which included CTNNB1, MAPK14, BTRC, EGFR, ADAM17. Pathway enrichment of HUB genes showed that they were dysregulated in carcinogenic and apoptotic pathways that seem to play a role in the progression of both the BCC. Conclusion: The result and findings of bioinformatic analysis highlighted the molecular pathways and genes enriched in both Eyelid BCC as well as Non- Ocular BCC. The identified pathways should be studied further to recognise common molecular events that would lead to the progression of BCC. This may provide a window to explore the prognostic and therapeutic strategies common to both BCC. Keywords: Basal cell carcinoma (BCC), Cancer, Microarray, Ophthalmology, Tumour marker


2021 ◽  
pp. 153537022110487
Author(s):  
Zirui Zhu ◽  
Rui Huang ◽  
Baojun Huang

Gastric cancer (GC) remains one of the most prevalent types of malignancies worldwide, and also one of the most reported lethal tumor-related diseases. Circular RNAs (circRNAs) have been certified to be trapped in multiple aspects of GC pathogenesis. Yet, the mechanism of this regulation is mostly undefined. This research is designed to discover the vital circRNA-microRNA (miRNA)-messenger RNA (mRNA) regulatory network in GC. Expression profiles with diverse levels including circRNAs, miRNAs, and mRNAs were all determined using microarray public datasets from Gene Expression Ominous (GEO). The differential circRNAs expressions were recognized against the published robust rank aggregation algorithm. Besides, a circRNA-based competitive endogenous RNA (ceRNA) interaction network was visualized via Cytoscape software (version 3.8.0). Functional and pathway enrichment analysis associated with differentially expressed targeted mRNAs were conducted using Cytoscape and an online bioinformatics database. Furthermore, an interconnected protein–protein interaction association network which consisted of 51 mRNAs was predicted, and hub genes were screened using STRING and CytoHubba. Then, several hub genes were chosen to explore their expression associated with survival rate and clinical stage in GEPIA and Kaplan-Meier Plotter databases. Finally, a carefully designed circRNA-related ceRNA regulatory subnetwork including four circRNAs, six miRNAs, and eight key hub genes was structured using the online bioinformatics tool.


Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 404 ◽  
Author(s):  
Claudia Cava ◽  
Gloria Bertoli ◽  
Isabella Castiglioni

Previous studies reported that Angiotensin converting enzyme 2 (ACE2) is the main cell receptor of SARS-CoV and SARS-CoV-2. It plays a key role in the access of the virus into the cell to produce the final infection. In the present study we investigated in silico the basic mechanism of ACE2 in the lung and provided evidences for new potentially effective drugs for Covid-19. Specifically, we used the gene expression profiles from public datasets including The Cancer Genome Atlas, Gene Expression Omnibus and Genotype-Tissue Expression, Gene Ontology and pathway enrichment analysis to investigate the main functions of ACE2-correlated genes. We constructed a protein-protein interaction network containing the genes co-expressed with ACE2. Finally, we focused on the genes in the network that are already associated with known drugs and evaluated their role for a potential treatment of Covid-19. Our results demonstrate that the genes correlated with ACE2 are mainly enriched in the sterol biosynthetic process, Aryldialkylphosphatase activity, adenosylhomocysteinase activity, trialkylsulfonium hydrolase activity, acetate-CoA and CoA ligase activity. We identified a network of 193 genes, 222 interactions and 36 potential drugs that could have a crucial role. Among possible interesting drugs for Covid-19 treatment, we found Nimesulide, Fluticasone Propionate, Thiabendazole, Photofrin, Didanosine and Flutamide.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jian Zhao ◽  
Xiaofeng Song ◽  
Tianyi Xu ◽  
Qichang Yang ◽  
Jingjing Liu ◽  
...  

Increasing lncRNA-associated competing triplets were found to play important roles in cancers. With the accumulation of high-throughput sequencing data in public databases, the size of available tumor samples is becoming larger and larger, which introduces new challenges to identify competing triplets. Here, we developed a novel method, called LncMiM, to detect the lncRNA–miRNA–mRNA competing triplets in ovarian cancer with tumor samples from the TCGA database. In LncMiM, non-linear correlation analysis is used to cover the problem of weak correlations between miRNA–target pairs, which is mainly due to the difference in the magnitude of the expression level. In addition, besides the miRNA, the impact of lncRNA and mRNA on the interactions in triplets is also considered to improve the identification sensitivity of LncMiM without reducing its accuracy. By using LncMiM, a total of 847 lncRNA-associated competing triplets were found. All the competing triplets form a miRNA–lncRNA pair centered regulatory network, in which ZFAS1, SNHG29, GAS5, AC112491.1, and AC099850.4 are the top five lncRNAs with most connections. The results of biological process and KEGG pathway enrichment analysis indicates that the competing triplets are mainly associated with cell division, cell proliferation, cell cycle, oocyte meiosis, oxidative phosphorylation, ribosome, and p53 signaling pathway. Through survival analysis, 107 potential prognostic biomarkers are found in the competing triplets, including FGD5-AS1, HCP5, HMGN4, TACC3, and so on. LncMiM is available at https://github.com/xiaofengsong/LncMiM.


2014 ◽  
Author(s):  
Mar Gonzàlez-Porta ◽  
Alvis Brazma

In the past years, RNA sequencing has become the method of choice for the study of transcriptome composition. When working with this type of data, several tools exist to quantify differences in splicing across conditions and to address the significance of those changes. However, the number of genes predicted to undergo differential splicing is often high, and further interpretation of the results becomes a challenging task. Here we present SwitchSeq, a novel set of tools designed to help the users in the interpretation of differential splicing events that affect protein coding genes. More specifically, we provide a framework to identify switch events, i.e., cases where, for a given gene, the identity of the most abundant transcript changes across conditions. The identified events are then annotated by incorporating information from several public databases and third-party tools, and are further visualised in an intuitive manner with the independent R package tviz. All the results are displayed in a self-contained HTML document, and are also stored in txt and json format to facilitate the integration with any further downstream analysis tools. Such analysis approach can be used complementarily to Gene Ontology and pathway enrichment analysis, and can also serve as an aid in the validation of predicted changes in mRNA and protein abundance. The latest version of SwitchSeq, including installation instructions and use cases, can be found at https://github.com/mgonzalezporta/SwitchSeq. Additionally, the plot capabilities are provided as an independent R package at https://github.com/mgonzalezporta/tviz.


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