scholarly journals Circular RNA Profiling and Bioinformatic Modeling Identify Its Regulatory Role in Hepatic Steatosis

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Xing-Ya Guo ◽  
Chong-Xin He ◽  
Yu-Qin Wang ◽  
Chao Sun ◽  
Guang-Ming Li ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Metabolic Pathways ◽  
Target Prediction ◽  
Principal Component ◽  
Circular Rna ◽  
Circular Rnas ◽  
Rna Profiling ◽  
Pathway Annotation ◽  
Wide Range ◽  
Chain Acyl

Circular RNAs (circRNAs) exhibit a wide range of physiological and pathological activities. To uncover their role in hepatic steatosis, we investigated the expression profile of circRNAs in HepG2-based hepatic steatosis induced by high-fat stimulation. Differentially expressed circRNAs were subjected to validation using QPCR and functional analyses using principal component analysis, hierarchical clustering, target prediction, gene ontology (GO), and pathway annotation, respectively. Bioinformatic integration established the circRNA-miRNA-mRNA regulatory network so as to identify the mechanisms underlying circRNAs’ metabolic effect. Here we reported that hepatic steatosis was associated with a total of 357 circRNAs. Enrichment of transcription-related GOs, especially GO: 0006355, GO: 004589, GO: 0045944, GO: 0045892, and GO: 0000122, demonstrated their specific actions in transcriptional regulation. Lipin 1 (LPIN1) was recognized to mediate the transcriptional regulatory effect of circRNAs on metabolic pathways. circRNA-miRNA-mRNA network further identified the signaling cascade of circRNA_021412/miR-1972/LPIN1, which was characterized by decreased level of circRNA_021412 and miR-1972-based inhibition of LPIN1. LPIN1-induced downregulation of long chain acyl-CoA synthetases (ACSLs) expression finally resulted in the hepatosteatosis. These findings identify circRNAs to be important regulators of hepatic steatosis. Transcription-dependent modulation of metabolic pathways may underlie their effects, partially by the circRNA_021412/miR-1972/LPIN1 signaling.

Circular RNA profiling reveals abundant and diverse circRNAs of SARS-CoV-2, SARS-CoV and MERS-CoV origin

2020 ◽  
Author(s):  
Shaomin Yang ◽  
Hong Zhou ◽  
Ruth Cruz-Cosme ◽  
Mingde Liu ◽  
Jiayu Xu ◽  
...  
Keyword(s):  
De Novo ◽  
Splice Junction ◽  
Circular Rna ◽  
Circular Rnas ◽  
Sequencing Data ◽  
Rna Profiling ◽  
Systematic Strategy ◽  
Coronavirus Infection ◽  
Abundance And Diversity ◽  
First Time

ABSTRACTCircular RNAs (circRNAs) encoded by DNA genomes have been identified across host and pathogen species as parts of the transcriptome. Accumulating evidences indicate that circRNAs play critical roles in autoimmune diseases and viral pathogenesis. Here we report that RNA viruses of the Betacoronavirus genus of Coronaviridae, SARS-CoV-2, SARS-CoV and MERS-CoV, encode a novel type of circRNAs. Through de novo circRNA analyses of publicly available coronavirus-infection related deep RNA-Sequencing data, we identified 351, 224 and 2,764 circRNAs derived from SARS-CoV-2, SARS-CoV and MERS-CoV, respectively, and characterized two major back-splice events shared by these viruses. Coronavirus-derived circRNAs are more abundant and longer compared to host genome-derived circRNAs. Using a systematic strategy to amplify and identify back-splice junction sequences, we experimentally identified over 100 viral circRNAs from SARS-CoV-2 infected Vero E6 cells. This collection of circRNAs provided the first line of evidence for the abundance and diversity of coronavirus-derived circRNAs and suggested possible mechanisms driving circRNA biogenesis from RNA genomes. Our findings highlight circRNAs as an important component of the coronavirus transcriptome.SummaryWe report for the first time that abundant and diverse circRNAs are generated by SARS-CoV-2, SARS-CoV and MERS-CoV and represent a novel type of circRNAs that differ from circRNAs encoded by DNA genomes.

scholarly journals Circular RNA Expression Profile and Analysis of Their Potential Function in Psoriasis

2018 ◽  
Vol 50 (1) ◽  
pp. 15-27 ◽  
Author(s):  
Meng Qiao ◽  
Jian Ding ◽  
Jianjun Yan ◽  
Ronghua Li ◽  
Jian Jiao ◽  
...  
Keyword(s):  
Target Prediction ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Healthy Skin ◽  
Go Analysis ◽  
Go Enrichment ◽  
New Perspective ◽  
Functional Analyses ◽  
Psoriatic Lesions

Background/Aims: Circular RNAs (circRNAs) are evolutionary conserved circular non-coding RNAs that play a role in several diseases by sequestering (sponging) microRNAs (miRNAs). However, their role in psoriasis remains unclear. In the present study, we investigated the expression of circRNAs and analyzed their potential functions in psoriasis. Methods: The SBC human ceRNA array V1.0 was used to analyze circRNA expression in psoriatic lesions and normal healthy skin tissues. Functional analyses were performed using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Putative miRNA response elements (MREs) were identified using miRNA target prediction software. Six upregulated circRNAs were verified by quantitative real-time reverse transcription polymerase chain reaction in psoriatic lesions and healthy skin tissues. Results: A total of 4956 circRNAs (3016 upregulated and 1940 downregulated; fold change ≥2 and p< 0.05) were identified as differentially expressed in psoriasis. Furthermore, 4405 MREs were identified among the differentially expressed circRNAs. hsa_circ_0061012 was upregulated in psoriatic lesions compared with normal healthy skin tissues. The top five MREs of hsa_circ_0061012 were hsa-miR-7157-5p, hsa-miR-4769-3p, hsa-miR-6817-5p, hsa-miR-4310, and hsa-miR-6882-3p. GO analysis was carried out to investigate the biological functions enriched among the upregulated targets of five miRNAs in psoriasis. The GO analysis identified that most of top 30 of GO enrichment are related to psoriasis. Conclusion: hsa_circ_0061012 might be a candidate biomarker for psoriasis. The results provide a new perspective for a better understanding of ceRNA-mediated gene regulation in psoriasis, and provide a novel theoretical basis for further studies on the function of circRNA in psoriasis.

scholarly journals Circular RNA Profiling by Illumina Sequencing via Template-Dependent Multiple Displacement Amplification

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Ashirbad Guria ◽  
Kavitha Velayudha Vimala Kumar ◽  
Nagesh Srikakulam ◽  
Anakha Krishnamma ◽  
Saibal Chanda ◽  
...  
Keyword(s):  
Illumina Sequencing ◽  
Multiple Displacement Amplification ◽  
Circular Rna ◽  
Circular Rnas ◽  
Functional Roles ◽  
Rna Profiling ◽  
Competitive Edge ◽  
Living Organisms ◽  
First Time ◽  
Human And Mouse

Circular RNAs (circRNAs) are newly discovered incipient non-coding RNAs with potential roles in disease progression in living organisms. Significant reports, since their inception, highlight the abundance and putative functional roles of circRNAs in every organism checked for, like O. sativa, Arabidopsis, human, and mouse. CircRNA expression is generally less than their linear mRNA counterparts which fairly explains the competitive edge of canonical splicing over non-canonical splicing. However, existing methods may not be sensitive enough for the discovery of low-level expressed circRNAs. By combining template-dependent multiple displacement amplification (tdMDA), Illumina sequencing, and bioinformatics tools, we have developed an experimental protocol that is able to detect 1,875 novel and known circRNAs from O. sativa. The same method also revealed 9,242 putative circRNAs in less than 40 million reads for the first time from the Nicotiana benthamiana whose genome has not been fully annotated. Supported by the PCR-based validation and Sanger sequencing of selective circRNAs, our method represents a valuable tool in profiling circRNAs from the organisms with or without genome annotation.

scholarly journals Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis

2017 ◽  
Vol 26 (18) ◽  
pp. 3564-3572 ◽  
Author(s):  
Leire Iparraguirre ◽  
Maider Muñoz-Culla ◽  
Iñigo Prada-Luengo ◽  
Tamara Castillo-Triviño ◽  
Javier Olascoaga ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Circular Rna ◽  
Circular Rnas ◽  
Rna Profiling ◽  
New Biomarkers

scholarly journals Comprehensive Circular RNA Profiling Reveals the Regulatory Role of the CircRNA-0067835/miR-155 Pathway in Temporal Lobe Epilepsy

2018 ◽  
Vol 51 (3) ◽  
pp. 1399-1409 ◽  
Author(s):  
Guo-Hua Gong ◽  
Feng-Mao An ◽  
Yu Wang ◽  
Ming Bian ◽  
Di Wang ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Circular Rna ◽  
Fine Tuning ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
G1 Arrest ◽  
Rna Profiling

Background/Aims: Temporal lobe epilepsy (TLE) is the most common form of adult localization-related epilepsy that is accompanied by progressive etiopathology and high incidences of drug resistance. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression, however, the expression profile and clinical significance of circRNAs in TLE remains unknown. Methods: Circular RNA microarray was conducted to identify TLE-related circRNAs. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in TLE in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in TLE cell. Results: 586 differentially expressed circRNAs were identified between TLE and the control tissues. The expression of circRNA-0067835 was significantly down-regulated in tissues and plasma from TLE patients. Lower circRNA-0067835 correlated to increased seizure frequency, HS, and higher Engel’s score. Overexpression of circRNA-0067835 observably decreased SH-SY5Y cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. Conclusion: Our experiments showed that circRNA-0067835 regulated refractory epilepsy progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with TLE.

scholarly journals Main Human Urinary Metabolites after Genipap (Genipa americana L.) Juice Intake

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1155 ◽  
Author(s):  
Livia Dickson ◽  
Mathieu Tenon ◽  
Ljubica Svilar ◽  
Pascale Fança-Berthon ◽  
Raphael Lugan ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Metabolic Pathways ◽  
High Resolution Mass Spectrometry ◽  
Principal Component ◽  
Urinary Metabolites ◽  
Human Consumption ◽  
Healthy Male ◽  
Wide Range ◽  
Before And After ◽  
First Time

Genipap (Genipa americana L.) is a native fruit from Amazonia that contains bioactive compounds with a wide range of bioactivities. However, the response to genipap juice ingestion in the human exposome has never been studied. To identify biomarkers of genipap exposure, the untargeted metabolomics approach in human urine was applied. Urine samples from 16 healthy male volunteers, before and after drinking genipap juice, were analyzed by liquid chromatography–high-resolution mass spectrometry. XCMS package was used for data processing in the R environment and t-tests were applied on log-transformed and Pareto-scaled data to select the significant metabolites. The principal component analysis (PCA) score plots showed a clear distinction between experimental groups. Thirty-three metabolites were putatively annotated and the most discriminant were mainly related to the metabolic pathways of iridoids and phenolic derivatives. For the first time, the bioavailability of genipap iridoids after human consumption is reported. Dihydroxyhydrocinnamic acid, (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate, hydroxyhydrocinnamic acid, genipic acid, 12-demethylated-8-hydroxygenipinic acid, 3(7)-dehydrogenipinic acid, genipic acid glucuronide, nonate, and 3,4-dihydroxyphenylacetate may be considered biomarkers of genipap consumption. Human exposure to genipap reveals the production of derivative forms of bioactive compounds such as genipic and genipinic acid. These findings suggest that genipap consumption triggers effects on metabolic signatures.

It is better an approximate answer to the right question than the exact answer to the wrong question : the case of the psychometric analysis of the ASQ:SE

2020 ◽  
Author(s):  
Luis Anunciacao ◽  
janet squires ◽  
J. Landeira-Fernandez
Keyword(s):  
Internal Structure ◽  
Statistical Methods ◽  
Principal Component ◽  
Psychological Theory ◽  
Published Data ◽  
Multivariate Statistical ◽  
Exact Answer ◽  
Wide Range ◽  
Ages And Stages Questionnaire ◽  
The Right

One of the main activities in psychometrics is to analyze the internal structure of a test. Multivariate statistical methods, including Exploratory Factor analysis (EFA) and Principal Component Analysis (PCA) are frequently used to do this, but the growth of Network Analysis (NA) places this method as a promising candidate. The results obtained by these methods are of valuable interest, as they not only produce evidence to explore if the test is measuring its intended construct, but also to deal with the substantive theory that motivated the test development. However, these different statistical methods come up with different answers, providing the basis for different analytical and theoretical strategies when one needs to choose a solution. In this study, we took advantage of a large volume of published data (n = 22,331) obtained by the Ages and Stages Questionnaire Social-Emotional (ASQ:SE), and formed a subset of 500 children to present and discuss alternative psychometric solutions to its internal structure, and also to its subjacent theory. The analyses were based on a polychoric matrix, the number of factors to retain followed several well-known rules of thumb, and a wide range of exploratory methods was fitted to the data, including EFA, PCA, and NA. The statistical outcomes were divergent, varying from 1 to 6 domains, allowing a flexible interpretation of the results. We argue that the use of statistical methods in the absence of a well-grounded psychological theory has limited applications, despite its appeal. All data and codes are available at https://osf.io/z6gwv/.

scholarly journals Comprehensive profiling analysis of the N6-methyladenosine-modified circular RNA transcriptome in cultured cells infected with Marek’s disease virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aijun Sun ◽  
Rui Wang ◽  
Shuaikang Yang ◽  
Xiaojing Zhu ◽  
Ying Liu ◽  
...  
Keyword(s):  
Disease Virus ◽  
Cultured Cells ◽  
Circular Rna ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Circular Rnas ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Pathway Analyses ◽  
Profiling Analysis

AbstractMarek’s disease virus (MDV) induces severe immunosuppression and lymphomagenesis in the chicken, its natural host, and results in a condition that investigated the pathogenesis of MDV and have begun to focus on the expression profiling of circular RNAs (circRNAs). However, little is known about how the expression of circRNAs is referred to as Marek’s disease. Previous reports have is regulated during MDV replication. Here, we carried out a comprehensive profiling analysis of N6-methyladenosine (m6A) modification on the circRNA transcriptome in infected and uninfected chicken embryonic fibroblast (CEF) cells. Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) revealed that m6A modification was highly conserved in circRNAs. Comparing to the uninfected group, the number of peaks and conserved motifs were not significantly different in cells that were infected with MDV, although reduced abundance of circRNA m6A modifications. However, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses revealed that the insulin signaling pathway was associated with the regulation of m6A modified circRNAs in MDV infection. This is the first report to describe alterations in the transcriptome-wide profiling of m6A modified circRNAs in MDV-infected CEF cells.

scholarly journals The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis

2021 ◽  
Author(s):  
Han-Wen Chen ◽  
Xiao-Xia Zhang ◽  
Zhu-Ding Peng ◽  
Zu-Min Xing ◽  
Yi-Wen Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Pain ◽  
Expression Profiles ◽  
Bone Cancer ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Bone Cancer Pain ◽  
Circular Rnas ◽  
Altered Expression ◽  
Proliferation And Apoptosis

AbstractTreatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.

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