scholarly journals Differential expression profiles and functional analysis of circular RNAs in children with fulminant myocarditis

Epigenomics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1129-1141 ◽  
Author(s):  
Li Zhang ◽  
Bo Han ◽  
Jing Wang ◽  
Qingqing Liu ◽  
Yaru Kong ◽  
...  

Aim: To assess differential expression profiles of circular RNAs (circRNAs) and explore their possible functions in children with fulminant myocarditis. Materials & methods: circRNA microarray experiments were carried out for determining differential expression profiles of circRNAs in three children with fulminant myocarditis and three healthy volunteers. Functional analysis and circRNA–miRNA–mRNA interaction network building were conducted to study biological functions. Results: This work identified 2281 upregulated and 892 downregulated circRNAs. Further assessment confirmed hsa_circ_0071542 upregulation (2.5-fold) in fulminant myocarditis. Functional analysis demonstrated the differentially expressed circRNAs mainly contributed to inflammation and immunity. Conclusion: circRNAs might have substantial roles in pediatric fulminant myocarditis, and hsa_circ_0071542 could serve as a promising biomarker.

2020 ◽  
Vol 7 ◽  
Author(s):  
Wei Sun ◽  
Bo Han ◽  
Dongxiao Cai ◽  
Jing Wang ◽  
Diandong Jiang ◽  
...  

Circular RNAs (circRNAs) have emerged as essential regulators and biomarkers in various diseases. To assess the different expression levels of circRNAs in pediatric dilated cardiomyopathy (PDCM) and explore their biological and mechanistic significance, we used RNA microarrays to identify differentially expressed circRNAs between three children diagnosed with PDCM and three healthy age-matched volunteers. The biological function of circRNAs was assessed with a circRNA–microRNA (miRNA)–mRNA interaction network constructed from Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in 25 children with PDCM and 25 healthy volunteers. We identified 257 up-regulated (fold change ≤ 0.5, P < 0.05) and 899 down-regulated (fold change ≥2, P < 0.05) circRNAs in PDCM patients when compared to healthy volunteers. The qRT-PCR experiments confirmed has_circ_0067735 down-regulation (0.45-fold, P < 0.001), has_circ_0070186 up-regulation (2.82-fold, P < 0.001), and has_circ_0069972 down-regulation (0.50-fold, P < 0.05). A functional analysis of these differentially expressed circRNAs suggests that they are associated with hypertrophy, remodeling, fibrosis, and autoimmunity. CircRNAs have been implicated in PDCM through largely unknown mechanisms. Here we report differentially expressed circRNAs in PDCM patients that may illuminate the mechanistic roles in the etiology of PDCM that could serve as non-invasive diagnostic biomarkers.


2021 ◽  
Vol 9 ◽  
Author(s):  
Dongxiao Cai ◽  
Bo Han ◽  
Wei Sun ◽  
Li Zhang ◽  
Jing Wang ◽  
...  

Aim: To evaluate the expression profile of long non-coding RNAs (lncRNAs) in different left ventricular function of dilated cardiomyopathy (DCM) in children and explore their possible functions.Methods: The lncRNA microarray experiment was used to determine the differential expression profile of lncRNA in three children with DCM and three healthy volunteers. The functional analysis and the construction of the lncRNA-mRNA interaction network were carried out to study the biological functions. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to verify the microarray data.Results: There were 369 up-regulated lncRNAs identified in the DCM patients (fold change >2, P < 0.05), and 505 down-regulated lncRNAs. Based on target gene prediction and co-expression network construction, 9 differentially expressed lncRNAs were selected for the PCR to verify the accuracy of the microarray data, of which 5 were up-regulated and 4 were down-regulated, and finally proved that 7 of them were consistent with the trend of microarray data results. Four of these lncRNAs had significant differences between the patients with poor cardiac function and patients with improved left ventricle function.Conclusion: LncRNAs may play an important role in pediatric DCM and may provide a new perspective for the pathogenesis, diagnosis, and treatment of this disease.


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.


2021 ◽  
Author(s):  
Bita Hassani ◽  
Hasan Mollanoori ◽  
Farkhondeh Pouresmaeili ◽  
Yazdan Asgari ◽  
Soudeh Ghafouri-Fard

Abstract Background. Luminal tumors are the utmost frequent subtype of breast cancer (BC). Despite luminal BC has relatively good prognosis, in a subset of patients, disease relapse occursto endocrine therapy ;hence, there is a critical need to identify new strategies to promote the early detection and more effective therapies. Noncoding RNAs including microRNAs, long noncoding RNAs, and circular RNAs can interact with and modulate each other via diverse molecular mechanisms and make a complicated regulatory network.ncRNAs participate in diverse biological processes and disorders such as breast tumors. Therefore, understanding their regulatory mechanisms allow to develop new field of research and therapeutic options for BC patients.Methods. In this study, BC-specific RNA expression profiles including mRNAs, miRNAs, lncRNAs, and circRNAs were retrievedfrom Gene Expression Omnibus microarray datasets, and differentially expressed(DE) items were obtained. Disease ontology, functional and pathway enrichment analyses were executed. The protein-protein interaction network was constructed, and hub mRNAs were extracted.The prognostic value of hub mRNAs in patients of BC were performed. Subsequently, a ceRNA network was established.Results. In total, 691 DE genes, 122 DE lncRNAs, 60 DE miRNAs, and 38 DE circRNAs in breast tumor samples were compared with normal samples. Subsequently, 12 hub-genesincluding FOXO3, RHOA, EZH2, KIT, HSP90B1, NCOA3, RAC1, IGF1, CAV1, CXCR4, CCNB1, and ITGB1 were screened from the network. Kaplan-Meier Plotter results revealed that FOXO3 and RHOA were a suitable prognostic marker for patients with breast cancer. Finally, we determined possible ncRNAs (circ0007535, circ0002727, circ0005240, circ0014130, circ0044927, circ0007001, circ0089153,NORAD, MALAT1, TUG1, ZFAS1, OPI5-AS1, miR183,miR182, miR101, miR200c, miR200b, miR149, miR342, and miR1207) which could crosstalk with each other to regulateFOXO3 and RHOA through different regulatory patterns. Conclusion. These data might improve our perception of the breast tumorigenesis and could develop new field of research and therapeutic options for BC patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Jinshan Suo ◽  
Xinling Xu ◽  
Haoyan Xu ◽  
Naifang Hou ◽  
Jiaming Zhang ◽  
...  

The aim of the study is to explore the expression profile variation of circular RNAs (circRNAs) in the peripheral blood of subjects with nonarteritic anterior ischemic optic neuropathy (NAION) and without NAION, to analyze the differential expression results, and to predict the role of circRNAs in disease development, providing novel ideas and methods for treatment and diagnosis. High-throughput sequencing to explore the expression profiles of RNAs in the peripheral blood of 6 NAION patients and 5 healthy controls was applied. Quality control obtained the advanced data from the original data by ticking out the unqualified data. Then, cluster analysis, volcano plot, coexpression network, and protein-protein interaction network (PPI) were performed. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to analyze the whole expressed genes. Lastly, the quantitative real-time Polymerase Chain Reaction (qRT-PCR) was used to verify those significantly differentially expressed circRNAs and do some bioinformatics analysis and prediction in 12 NAION patients and 12 controls. There were significant differences in the expression of 49 circRNAs in the peripheral blood of NAION patients, in which there were 24 upregulations and 25 downregulations (variation folds > 2 and P < 0.05 ), and it was confirmed that hsa_circ_0005583, hsa_circ_0003922, hsa_circ_0002021, and hsa_circ_0000462 were significantly downregulated (variation folds > 2 and P < 0.05 ), especially hsa_circ_0005583 which was the most significantly changed one ( P < 0.001 ), and are related to processes such as neurodegeneration, oxidative stress, immunity, and metabolism. The expression profile of circRNAs in the peripheral blood of NAION patients is significantly changed, enriching our understanding of the disease.


2021 ◽  
Vol 49 (2) ◽  
pp. 94-103
Author(s):  
Jie Chen ◽  
Xiyan Xiao ◽  
Shan He ◽  
Yi Qiao ◽  
Shuwei Ma

Background: Emerging evidence shows that circular RNAs (circRNAs) participate in the pathogenesis of multiple immune diseases. However, few studies have focused on the mechanisms of circRNAs involved in allergic rhinitis (AR). Methods: This study performed an RNA sequence (RNA-seq) profiling to identify the expression of circRNAs in nasal mucosa from ovalbumin-induced AR murine models and normal controls. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) was then conducted to validate the differential expression of circRNAs. Bioinformatics analysis was applied to demonstrate the biological functions of the dysregulated circRNAs. Results: A total of 86 distinct circRNA candidates were sequenced, of which 51 were upregulated and 35 were downregulated. The T cell receptor, B cell receptor, and calcium signaling pathways may be involved in the pathology of AR. Furthermore, a circRNA-miRNA interaction network was constructed via miRNA response elements analysis. Some circRNAs were cor-related with miRNAs that are involved in T cell polarization and activation, thereby highlighting their potential role in the pathogenesis of AR. Conclusions: This study demonstrates a number of aberrantly expressed circRNAs related to AR, and offers a novel perspective into AR pathogenesis and future therapeutic strategies.


Epigenomics ◽  
2021 ◽  
Author(s):  
Jing Wang ◽  
Bo Han ◽  
Yingchun Yi ◽  
Yan Wang ◽  
Li Zhang ◽  
...  

Aim: Fulminant myocarditis (FM) has neither validated biomarkers nor well-established therapy. Roles of tRNA-derived small RNAs (tsRNAs) in FM remain unknown. Materials & methods: Small RNA sequencing was conducted in plasma from children with FM during acute and convalescent phase and matched healthy volunteers. Data were validated by quantitative real-time PCR in larger sample-sized groups and in vitro. Functional analysis was performed to explore the roles. Results: tiRNA-Gln-TTG-001 was overexpressed in children with FM during acute phase, and the generation and extracellular release of tiRNA-Gln-TTG-001 were higher after myocarditis-mimicked activity in vitro. Several pathways might participate in the pathogenesis of FM. Conclusion: tsRNAs may play an important role in FM, and tiRNA-Gln-TTG-001 might represent a novel and promising biomarker and therapeutic target.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lianghai Wang ◽  
Lisha Zhou ◽  
Jun Hou ◽  
Jin Meng ◽  
Ke Lin ◽  
...  

Abstract Background The regulatory roles of circular RNAs (circRNAs) in tumorigenesis have attracted increasing attention. However, novel circRNAs with the potential to be used as serum/plasma biomarkers and their regulatory mechanism in the pathogenesis of hepatocellular carcinoma (HCC) remain explored. Methods CircRNA expression profiles of tumor tissues and plasma samples from HCC patients were compiled and jointly analyzed. CircRNA–miRNA–mRNA interactions were predicted by bioinformatics tools. The expression of interacting miRNAs and mRNA was verified in independent datasets. Survival analysis and pathway enrichment analysis were conducted on hub genes. Results We identified three significantly up-regulated circRNAs (hsa_circ_0009910, hsa_circ_0049783, and hsa_circ_0089172) both in HCC tissues and plasma samples. Two of them were validated to be indeed circular and could be excreted from hepatoma cells. We further revealed four miRNAs (hsa-miR-455-5p, hsa-miR-615-3p, hsa-miR-18a-3p, hsa-miR-4524a-3p) that targeting circRNAs and expressed in human HCC samples, and 95 mRNAs targeted by miRNAs and significantly up-regulated in two HCC cohorts. A protein-protein interaction network revealed 19 hub genes, 12 of them (MCM6, CCNB1, CDC20, NDC80, ZWINT, ASPM, CENPU, MCM3, MCM5, ECT2, CDC7, and DLGAP5) were associated with reduced survival in two HCC cohorts. KEGG, Reactome, and Wikipathway enrichment analysis indicated that the hub genes mainly functioned in DNA replication and cell cycle. Conclusions Our study uncovers three novel deregulated circRNAs in tumor and plasma from HCC patients and provides an insight into the pathogenesis from the circRNA–miRNA–mRNA regulatory network.


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