scholarly journals A genome-wide circular RNA transcriptome in Rat

2021 ◽  
Author(s):  
Disha Sharma ◽  
Paras Sehgal ◽  
Sridhar Sivasubbu ◽  
Vinod Scaria
Keyword(s):  
Developmental Stages ◽  
Donor Site ◽  
Model Organism ◽  
Circular Rna ◽  
Development Stage ◽  
Model Organisms ◽  
Circular Rnas ◽  
Tissue Samples ◽  
A Genome ◽  
The Difference

Abstract Circular RNAs are a novel class of non-coding RNAs that backsplice from 5' donor site and 3' acceptor sites to form a circular structure. A number of circRNAs have been discovered in model organisms including human, mouse, Drosophila, among other organisms. There are a few candidate-based studies on circular RNAs in rat, a well-studied model organism as well. A number of pipelines have been published to identify the back splice junctions for the discovery of circRNAs but studies comparing these tools have suggested that a combination of tools would be a better approach to identify high-confidence circular RNAs. The availability of a recent dataset of transcriptomes encompassing 11 tissues, 4 developmental stages and 2 genders motivated us to explore the landscape of circular RNAs in the organism in this context. In order to understand the difference among different pipelines, we employed 5 different combinations of tools to identify circular RNAs from the dataset. We compared the results of the different combination of tools/pipelines with respect to alignment, total number of circRNAs identified and read-coverage. In addition, we identified tissue-specific, development-stage specific and gender-specific circular RNAs and further independently validated 16 circRNA junctions out of 24 selected candidates in 5 tissue samples and estimated the quantitative expression of 5 circRNA candidates using real-time PCR and our analysis suggests 3 candidates as tissue-enriched. This study is one of the most comprehensive studies that provides a map of circular RNA transcriptome as well as to understand the difference among different computational pipelines in Rat.

scholarly journals A genome-wide circular RNA transcriptome in Rat

2021 ◽  
Author(s):  
Disha Sharma ◽  
Paras Sehgal ◽  
Sridhar Sivasubbu ◽  
Vinod Scaria
Keyword(s):  
Developmental Stages ◽  
Donor Site ◽  
Model Organism ◽  
Circular Rna ◽  
Model Organisms ◽  
Circular Rnas ◽  
Acceptor Site ◽  
Tissue Samples ◽  
A Genome ◽  
The Difference

AbstractBackgroundCircular RNAs are a novel class of non-coding RNAs that backsplice from 5’ donor site and 3’ acceptor site to form a circular structure. A number of circRNAs have been discovered in model organisms including human, mouse, Drosophila, among other organisms. There are a few candidate-based studies on circular RNAs in rat, a well studied model organism. The availability of a recent dataset of transcriptomes encompassing 11 tissues, 4 developmental stages and 2 genders motivated us to explore the landscape of circular RNAs in the organism.MethodologyIn order to understand the difference among different pipelines, we have used the same bodymap RNA sequencing dataset. A number of pipelines have been published to identify the backsplice junctions for the discovery of circRNAs but studies comparing these tools have suggested that a combination of tools would be a better approach to identify high-confidence circular RNAs. We employed 5 different combinations of tools including tophat_CIRCexplorer2, segemehl_CIRCexplorer2, star_CIRCexplorer, Bowtie2_findcirc and Bowtie2_findcirc (noHisat2) to identify circular RNAs from the dataset.ResultsOur analysis identified a number of tissue-specific, developmental stage specific and gender specific circular RNAs. We further independently validated 16 circRNA junctions out of 24 selected candidates in 5 tissue samples. We additionally estimated the quantitative expression of 5 circRNA candidates using real-time PCR and our analysis suggests 3 candidates as tissue-enrichedConclusionThis study is one of the most comprehensive studies that provides a circular RNA transcriptome as well as to understand the difference among different computational pipelines in Rat.

scholarly journals Genome-Wide Perturbations of Alu Expression and Alu-Associated Post-Transcriptional Regulations Find a Uniqueness in Oligodendroglioma

2021 ◽  
Author(s):  
Taeyoung Hwang ◽  
Sojin Kim ◽  
Tamrin Chowdhury ◽  
Hyeon Jong Yu ◽  
Kyung-Min Kim ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Regulatory Element ◽  
Circular Rna ◽  
Circular Rnas ◽  
Global Changes ◽  
Rna Seq ◽  
Tissue Samples ◽  
Genome Wide ◽  
A Genome

Abstract BackgroundAlu is a primate-specific repeat element in the human genome and has been increasingly appreciated as a regulatory element in many biological processes. But the role of Alu has not been studied comprehensively in brain tumor because an evolutionary perspective has been the subject of little research in brain tumor. We aim to investigate the relevance of Alu to the gliomagenesis.MethodsUsing a total of 41 pairs of neurotypicial brain tissue samples and samples of diverse gliomas, we performed strand-specific RNA-seq and analyzed two Alu-associated post-transcriptional regulations, A-to-I editing and circular RNAs, and Alu expression in a genome-wide way. ResultsWe found that while both A-to-I editing and circular RNA are decreased overall in gliomas, grade 2 oligodendrogliomas do not show this same pattern of global changes. Instead, in comparison with other gliomas, oligodendrogliomas showed a higher proportion of perturbed Alu RNA. Adenosine deaminase acting on RNA 2 (ADAR2) was down-regulated in gliomas other than grade 2 oligodendrogliomas, contributing to the observed Alu-associated perturbation. ConclusionsOur results demonstrate that Alu is associated with glioma development and grade 2 oligodendroglioma exhibits a unique pattern of Alu-associated post-transcriptional regulations, which provides an insight to gliomagenesis from the perspective of an evolutionary genetic element.

scholarly journals Circular RNA circCCDC66 Contributes to Malignant Phenotype of Osteosarcoma by Sponging miR-338-3p to Upregulate the Expression of PTP1B

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Deng Xiang ◽  
Yugang Li ◽  
Yanshui Lin
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanism ◽  
Cell Lines ◽  
Rapid Development ◽  
Circular Rna ◽  
Molecular Medicine ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Tissue Samples

In recent years, the mechanism of cancer research has become hotspots of life science and medicine, especially due to the rapid development of molecular medicine and bioinformatics research. Similarly, the molecular mechanism also has received increasing attention in osteosarcoma (OS) research. Also, a considerable amount of research confirmed that circular RNAs (circRNAs) could regulate cancer cell growth and metastasis. This study aimed to explore the effect of a circRNA, circCCDC66, on OS and reveal its potential molecular mechanism. High circCCDC66 expression level was found in OS patient-derived tissue samples and OS cell lines by qRT-PCR. The abilities cell proliferation and metastatic of U2OS and SW1353 cells were then assessed by Cell Counting Kit-8 and transwell assay, respectively. The interaction between circCCDC66 and its target miRNAs were verified by the dual-luciferase reporter assay. Through functional experiments, we found that circCCDC66 knockdown promoted the inhibition of cell proliferation and metastatic of OS cell lines. From mechanistic perspective, circCCDC66 upregulated PTP1B by sponging miR-338-3p. Collectively, our findings demonstrated that circCCDC66 contributed to malignant behaviors of OS cells by miR-338-3p/PTP1B pathway, which suggested circCCDC66/miR-338-3p/PTP1B axis might be a potential therapeutic target.

Ontogenetic development of the otic region in the new model organism, Leucoraja erinacea (Chondrichthyes; Rajidae)

2018 ◽  
Vol 109 (1-2) ◽  
pp. 105-114 ◽  
Author(s):  
Cathrin PFAFF ◽  
Jürgen KRIWET ◽  
Kyle MARTIN ◽  
Zerina JOHANSON
Keyword(s):  
Soft Tissues ◽  
Developmental Stages ◽  
Model Organism ◽  
Model Organisms ◽  
Biological Research ◽  
Developmental Studies ◽  
Micro Computed Tomography ◽  
Computed Tomography Scanning ◽  
Cartilaginous Fishes ◽  
Tomography Scanning

ABSTRACTCartilaginous fishes have a long evolutionary history dating back 440 million years and include model organisms in a number of fields of biological research. However, comparative developmental studies of these organisms, particularly neuroanatomical investigations, still remain sparse. Here, pre-hatching to adult developmental stages of the Little Skate, Leucoraja erinacea, are investigated using micro-computed tomography scanning in conjunction with staining procedures designed to improve visualisation of soft tissues. Within the ear, the anatomy of the skeletal labyrinth changes during ontogeny and differs substantially from the underlying membranous system, contrary to previous observations in sharks. Additionally, substantial morphological remodelling characterises the parietal fossa, which appears initially as a massive and hook-like structure and subsequently becomes slender and surrounded by soft tissue. The sizes of the vestibular system and neurocranium increase isometrically from pre- to post-hatching phases, and then exponentially after the post-hatching stages.

scholarly journals Development of Leishmania (Mundinia) in guinea pigs

2019 ◽  
Author(s):  
Tomáš Bečvář ◽  
Padet Siriyasatien ◽  
Paul Bates ◽  
Petr Volf ◽  
Jovana Sádlová
Keyword(s):  
Guinea Pigs ◽  
Model Organism ◽  
Model Organisms ◽  
Control Group ◽  
Post Inoculation ◽  
Sand Flies ◽  
Tissue Samples ◽  
Wild Mammals ◽  
Reservoir Hosts ◽  
Lutzomyia Migonei

Abstract BackgroundLeishmaniasis is a human and animal disease caused by parasites of the genus Leishmania, which is now divided into 4 subgenera – L. (Leishmania), L. (Viannia), L. (Sauroleishmania) and L. (Mundinia). Subgenus Mundinia, established in 2016, is geographically widely dispersed, its distribution covers all continents, except Antarctica. It consists of 5 species - L. enriettii and L. macropodum are parasites of wild mammals while L. martiniquensis, L. orientalis and unnamed L. sp. from Ghana are infectious to humans. There is very little information on natural reservoir hosts and vectors for any Mundinia species. MethodsExperimental infections of guinea-pigs with all five Mundinia species were performed. Animals were injected intradermally with 107 culture-derived promastigotes into both ear pinnae. The courses of infections were monitored weakly; xenodiagnoses were performed at weeks 4 and 8 post infection using Lutzomyia migonei. The distribution of parasites in different tissues was determined post mortem by conventional PCR.ResultsNo significant differences in weight were observed between infected animals and the control group. Animals infected with L. enriettii developed temporary lesions at the site of inoculation and were infectious to Lu. migonei in xenodiagnoses. Animals infected with L. martiniquensis and L. orientalis developed temporary erythema and dry lesions at the site of inoculation, respectively, but were not infectious to sand flies. Guinea pigs infected by L. macropodum and L. sp. from Ghana showed no signs of infection during experiments, were not infectious to sand flies and leishmanial DNA was not detected in their tissue samples at the end of experiments at week 12 post-inoculation.ConclusionsAccording to our results, guinea pigs are not an appropriate model organism for studying Mundinia species other than L. enriettii. We suggest that for better understanding of L. (Mundinia) biology it is necessary to focus on other model organisms.

scholarly journals Circular RNAs in Clear Cell Renal Cell Carcinoma: Their Microarray-Based Identification, Analytical Validation, and Potential Use in a Clinico-Genomic Model to Improve Prognostic Accuracy

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1473 ◽  
Author(s):  
Franz ◽  
Ralla ◽  
Weickmann ◽  
Jung ◽  
Rochow ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Cox Regression ◽  
Clear Cell ◽  
Information Criteria ◽  
Circular Rnas ◽  
Cell Renal Cell Carcinoma ◽  
Tissue Samples ◽  
Cox Regression Analysis ◽  
Genome Wide ◽  
A Genome

Circular RNAs (circRNAs) may act as novel cancer biomarkers. However, a genome-wide evaluation of circRNAs in clear cell renal cell carcinoma (ccRCC) has yet to be conducted. Therefore, the objective of this study was to identify and validate circRNAs in ccRCC tissue with a focus to evaluate their potential as prognostic biomarkers. A genome-wide identification of circRNAs in total RNA extracted from ccRCC tissue samples was performed using microarray analysis. Three relevant differentially expressed circRNAs were selected (circEGLN3, circNOX4, and circRHOBTB3), their circular nature was experimentally confirmed, and their expression—along with that of their linear counterparts—was measured in 99 malignant and 85 adjacent normal tissue samples using specifically established RT-qPCR assays. The capacity of circRNAs to discriminate between malignant and adjacent normal tissue samples and their prognostic potential (with the endpoints cancer-specific, recurrence-free, and overall survival) after surgery were estimated by C-statistics, Kaplan-Meier method, univariate and multivariate Cox regression analysis, decision curve analysis, and Akaike and Bayesian information criteria. CircEGLN3 discriminated malignant from normal tissue with 97% accuracy. We generated a prognostic for the three endpoints by multivariate Cox regression analysis that included circEGLN3, circRHOBT3 and linRHOBTB3. The predictive outcome accuracy of the clinical models based on clinicopathological factors was improved in combination with this circRNA-based signature. Bootstrapping as well as Akaike and Bayesian information criteria confirmed the statistical significance and robustness of the combined models. Limitations of this study include its retrospective nature and the lack of external validation. The study demonstrated the promising potential of circRNAs as diagnostic and particularly prognostic biomarkers in ccRCC patients.

Circular RNA-based biomarkers in blood of patients with Fabry disease and related phenotypes

2021 ◽  
pp. jmedgenet-2020-107086
Author(s):  
Albina Nowak ◽  
George Haddad ◽  
Andreas D Kistler ◽  
Stellor Nlandu-Khodo ◽  
Felix Beuschlein ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Fabry Disease ◽  
Kidney Injury ◽  
Circular Rna ◽  
Therapeutic Monitoring ◽  
Circular Rnas ◽  
Lysosomal Storage ◽  
Predictive Values ◽  
Clinical Patient ◽  
A Genome

BackgroundFabry disease is a rare X-linked lysosomal storage disease caused by mutations in the galactosidase α gene. Deficient activity of α-galactosidase A leads to glycosphingolipid accumulations in multiple organs. Circular RNAs represent strong regulators of gene expression. Their circular structure ensures high stability in blood. We hypothesised that blood-based circular RNA profiles improve phenotypic assignment and therapeutic monitoring of Fabry disease.MethodsA genome-wide circular RNA expression analysis was performed in blood of genetically diagnosed patients with Fabry disease (n=58), age-matched and sex-matched healthy volunteers (n=14) and disease control patients with acute kidney injury (n=109). Most highly dysregulated circular RNAs were validated by quantitative real-time PCR. Circular RNA biomarker sensitivity, specificity, predictive values and area under the curve (AUC) were determined. Linear regression analyses were conducted for validated circular RNA biomarkers and clinical patient characteristics.ResultsA distinct circular RNA transcriptome signature identified patients with Fabry disease. Level of circular RNAs hsa_circ_0006853 (AUC=0.73), hsa_circ_0083766 (AUC=0.8) and hsa_circ_0002397 (AUC=0.8) distinguished patients with Fabry disease from both healthy controls and patients with acute kidney injury. Hsa_circ_0002397 was, furthermore, female-specifically expressed. Circular RNA level were significantly related to galactosidase α gene mutations, early symptoms, phenotypes, disease severities, specific therapies and long-term complications of Fabry disease.ConclusionThe discovery of circular RNA-based and Fabry disease–specific biomarkers may advance future diagnosis of Fabry disease and help to distinguish related phenotypes.

Circular RNA Circ-0006302 Promotes the Growth, Migration, and Invasion of Cholangiocarcinoma Cells by Regulating the Mir-1299/PD-L1 Axis as a Competing Endogenous RNA

2021 ◽  
Author(s):  
Weiqian Chen ◽  
Liyun Zheng ◽  
Songquan Wu ◽  
Chenying Lu ◽  
Bufu Tang ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
The Difference ◽  
Gain Loss

Abstract Background: Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis, with no effective therapy other than surgical resection. Circular RNAs (circRNAs) serve as a brand-new class of transcription products among abundant cancer processes. Nevertheless, the mechanisms account for their modification in CCA remain unknown. Methods: First, microarray sequencing was applied to detect the difference of circRNAs expression between CCA and corresponding non-tumor tissues. We utilized qRT-PCR to measure circ-0006302 levels in CCA cells and specimens. Gain/loss of-function assays and animal model of CCA were performed for the purpose of revealing the functions of circ-0006302 on the invasion, migration, and proliferation of CCA. We performed dual luciferase reporter, RNA-FISH and rescue assays for clarifying the mechanism behind. Results: In CCA tissues and cell lines circ-0006302 was highly expressed relatively. In vitro, overexpression of circ-0006302 intensifies the epithelial-to-mesenchymal transition (EMT) and the invasion, migration, and growth of CCA cells; and intensifies the growth as well as metastasis of tumors in a CCA mouse model. Furthermore, it was elucidated that circ-0006302 sponged miR-1299 to upregulate PD‐L1 expression. Through the process above, circ-0006302 binds to miR-1299 and emancipates PD-L1, facilitating the invasion, migration, and proliferation in CCA cells. Momentously, the results obtained revealed that circ-0006302 silencing elevated the expression of interferon (IFN)‐γ, and interleukin (IL)‐4 but diminished the IL-10 expression, while these effects could be reversed by miR-1299 inhibitor.Conclusion: circ-0006302 silence blocked the CCA progression via intensifying miR‐1299‐targeted downregulation of PD‐L1. Our conclusion provides novel therapeutic tactics for treating this fatal disease.

scholarly journals Identification and characterization of circular RNAs in Ganoderma lucidum

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Junjie Shao ◽  
Liqiang Wang ◽  
Xinyue Liu ◽  
Meng Yang ◽  
Haimei Chen ◽  
...  
Keyword(s):  
Ganoderma Lucidum ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Circular Rnas ◽  
Rna Seq ◽  
Polysaccharide Biosynthesis ◽  
Genome Wide ◽  
A Genome ◽  
Positive Correlations

Abstract Circular RNAs (circRNAs) play important roles in animals, plants, and fungi. However, no circRNAs have been reported in Ganoderma lucidum. Here, we carried out a genome-wide identification of the circRNAs in G.lucidum using RNA-Seq data, and analyzed their features. In total, 250 and 2193 circRNAs were identified from strand-specific RNA-seq data generated from the polyA(−) and polyA(−)/RNase R-treated libraries, respectively. Six of 131 (4.58%) predicted circRNAs were experimentally confirmed. Across three developmental stages, 731 exonic circRNAs (back spliced read counts ≥ 5) and their parent genes were further analyzed. CircRNAs were preferred originating from exons with flanking introns, and the lengths of the flanking intron were longer than those of the control introns. A total of 200 circRNAs were differentially expressed across the three developmental stages of G. lucidum. The expression profiles of 119 (16.3%) exonic circRNAs and their parent genes showed significant positive correlations (r ≥ 0.9, q < 0.01), whereas 226 (30.9%) exonic circRNAs and their parent genes exhibited significant negative correlations (r ≤ −0.9, q < 0.01), in which 53 parent genes are potentially involved in the transcriptional regulation, polysaccharide biosynthesis etc. Our results indicated that circRNAs are present in G. lucidum, with potentially important regulatory roles.

scholarly journals Circular RNA circUBE2J2 acts as the sponge of microRNA-370-5P to suppress hepatocellular carcinoma progression

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Lu Zhang ◽  
Yachong Liu ◽  
Haisu Tao ◽  
He Zhu ◽  
Yonglong Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Analysis ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Tissue Samples ◽  
Clinical Prognosis ◽  
Kaplan Meier ◽  
And Migration ◽  
Hcc Cells

AbstractAccumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in hepatocellular carcinoma is largely unknown. CircRNA microarray was performed to identify abnormally expressed circRNAs in HCC tissue samples. We conducted Kaplan–Meier survival analysis to explore the significance of circUBE2J2 in clinical prognosis. Then, we examined the functions of circUBE2J2 in HCC by cell proliferation, migration, and mouse xenograft assay. We identified miR-370-5P as a circUBE2J2-related microRNA by using biotin-labeled circUBE2J2 probe to perform RNA antisense purification (RAP) assay in HCC cells. The dual luciferase reporter assay and RNA pulldown assays were employed to verify the relationships among circUBE2J2, miRNA-370-5P, and KLF7. Microarray analysis and qRT-PCR verified a circRNA termed circUBE2J2 that was downregulated in HCC. Kaplan–Meier survival analysis showed that downregulated circUBE2J2 was correlated with poorer survival. CircUBE2J2 expression in HCC cells was selectively regulated via luciferase reporter assays; circUBE2J2 and KLF7 were observed to directly bind to miR-370-5P. Furthermore, knockdown of circUBE2J2 in HCC could downregulate KLF7, the target of miR-370-5P, thus promoting the proliferation and migration of HCC cells. Then the related experiment suggested that circUBE2J2 could regulate the expression of KLF7 by sponging miR-370-5p. In summary, we infer that circUBE2J2 may act as a competing endogenous RNA (ceRNA) to regulate KLF7 expression through sponging miR-370-5P and play a regulatory functions in HCC. CircUBE2J2 may be a diagnostic biomarker and potential target for HCC therapy.

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