scholarly journals BodyMap transcriptomes reveal unique circular RNA features across tissue types and developmental stages

2018 ◽  
Author(s):  
Tong Zhou ◽  
Xueying Xie ◽  
Musheng Li ◽  
Junchao Shi ◽  
Jin J. Zhou ◽  
...  
Keyword(s):  
Tissue Specificity ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Circular Rna ◽  
Circular Rnas ◽  
Comprehensive Investigation ◽  
Age Dependent ◽  
Regulatory Rnas ◽  
By Products ◽  
Cognate Mrnas

SummaryCircular RNAs (circRNAs) are a novel class of regulatory RNAs. Here, we present a comprehensive investigation of circRNA expression profiles across 11 tissues and 4 developmental stages in rats, along with cross-species analyses in humans and mice. Although positively correlated, circRNAs exhibit higher tissue specificity than cognate mRNAs. Also, genes with higher expression levels exhibit a larger fraction of spliced circular transcripts than their linear counterparts. Intriguingly, while we observed a monotonic increase of circRNA abundance with age in the rat brain, we further discovered a dynamic, age-dependent pattern of circRNA expression in the testes that is characterized by a dramatic increase with advancing stages of sexual maturity and a decrease with aging. The age-sensitive testicular circRNAs are highly associated with spermatogenesis, independent of cognate mRNA expression. The tissue/age implications of circRNAs suggest that they present unique physiological functions rather than simply occurring as occasional by-products of gene transcription.

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.

scholarly journals Expression Profiling and Functional Analysis of Circular RNAs in Inner Mongolian Cashmere Goat Hair Follicles

2021 ◽  
Vol 12 ◽  
Author(s):  
Fangzheng Shang ◽  
Yu Wang ◽  
Rong Ma ◽  
Zhengyang Di ◽  
Zhihong Wu ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Signaling Pathway ◽  
Expression Profiling ◽  
Regulatory Network ◽  
Expression Profiles ◽  
Circular Rna ◽  
Hair Follicles ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Cashmere Goats

BackgroundInner Mongolian cashmere goats have hair of excellent quality and high economic value, and the skin hair follicle traits of cashmere goats have a direct and important effect on cashmere yield and quality. Circular RNA has been studied in a variety of tissues and cells.ResultIn this study, high-throughput sequencing was used to obtain the expression profiles of circular RNA (circRNA) in the hair follicles of Inner Mongolian cashmere goats at different embryonic stages (45, 55, 65, and 75 days). A total of 21,784 circRNAs were identified. At the same time, the differentially expressed circRNA in the six comparison groups formed in the four stages were: d75vsd45, 59 upregulated and 33 downregulated DE circRNAs; d75vsd55, 61 upregulated and 102 downregulated DE circRNAs; d75vsd65, 32 upregulated and 33 downregulated DE circRNAs; d65vsd55, 67 upregulated and 169 downregulated DE circRNAs; d65vsd45, 96 upregulated and 63 downregulated DE circRNAs; and d55vsd45, 76 upregulated and 42 downregulated DE circRNAs. Six DE circRNA were randomly selected to verify the reliability of the sequencing results by quantitative RT-PCR. Subsequently, the circRNA corresponding host genes were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The results showed that the biological processes related to hair follicle growth and development enriched by GO mainly included hair follicle morphogenesis and cell development, and the signaling pathways related to hair follicle development included the Notch signaling pathway and NF-κB signaling pathway. We combined the DE circRNA of d75vsd45 with miRNA and mRNA databases (unpublished) to construct the regulatory network of circRNA–miRNA–mRNA, and formed a total of 102 pairs of circRNA–miRNA and 126 pairs of miRNA–mRNA interactions. The binding relationship of circRNA3236–chi-miR-27b-3p and circRNA3236–chi-miR-16b-3p was further verified by dual-luciferase reporter assays, and the results showed that circRNA3236 and chi-miR-27b-3p, and circRNA3236 and chi-miR-16b-3p have a targeted binding relationship.ConclusionTo summarize, we established the expression profiling of circRNA in the fetal skin hair follicles of cashmere goats, and found that the host gene of circRNA may be involved in the development of hair follicles of cashmere goats. The regulatory network of circRNA–miRNA–mRNA was constructed and preliminarily verified using DE circRNAs.

scholarly journals The Landscape of MicroRNA, Piwi-Interacting RNA, and Circular RNA in Human Saliva

2015 ◽  
Vol 61 (1) ◽  
pp. 221-230 ◽  
Author(s):  
Jae Hoon Bahn ◽  
Qing Zhang ◽  
Feng Li ◽  
Tak-Ming Chan ◽  
Xianzhi Lin ◽  
...  
Keyword(s):  
Body Fluid ◽  
Expression Profiles ◽  
Embryonic Stem ◽  
Bioinformatic Analysis ◽  
Circular Rna ◽  
Human Saliva ◽  
Body Fluids ◽  
Individual Variability ◽  
Circular Rnas ◽  
Rna Seq

Abstract BACKGROUND Extracellular RNAs (exRNAs) in human body fluids are emerging as effective biomarkers for detection of diseases. Saliva, as the most accessible and noninvasive body fluid, has been shown to harbor exRNA biomarkers for several human diseases. However, the entire spectrum of exRNA from saliva has not been fully characterized. METHODS Using high-throughput RNA sequencing (RNA-Seq), we conducted an in-depth bioinformatic analysis of noncoding RNAs (ncRNAs) in human cell-free saliva (CFS) from healthy individuals, with a focus on microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), and circular RNAs (circRNAs). RESULTS Our data demonstrated robust reproducibility of miRNA and piRNA profiles across individuals. Furthermore, individual variability of these salivary RNA species was highly similar to those in other body fluids or cellular samples, despite the direct exposure of saliva to environmental impacts. By comparative analysis of >90 RNA-Seq data sets of different origins, we observed that piRNAs were surprisingly abundant in CFS compared with other body fluid or intracellular samples, with expression levels in CFS comparable to those found in embryonic stem cells and skin cells. Conversely, miRNA expression profiles in CFS were highly similar to those in serum and cerebrospinal fluid. Using a customized bioinformatics method, we identified >400 circRNAs in CFS. These data represent the first global characterization and experimental validation of circRNAs in any type of extracellular body fluid. CONCLUSIONS Our study provides a comprehensive landscape of ncRNA species in human saliva that will facilitate further biomarker discoveries and lay a foundation for future studies related to ncRNAs in human saliva.

scholarly journals Expression Profile of Circular RNAs in Epicardial Adipose Tissue in Heart Failure

2019 ◽  
Author(s):  
Meili Zheng ◽  
Lei Zhao ◽  
Xinchun Yang
Keyword(s):  
Heart Failure ◽  
Adipose Tissue ◽  
Expression Profile ◽  
Epicardial Adipose Tissue ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Circular Rna ◽  
Circular Rnas ◽  
Artery Disease ◽  
Pathway Analyses

AbstractRecent studies have reported circular RNA (circRNA) expression profiles in various tissue types; specifically, a recent work showed a detailed circRNA expression landscape in the heart. However, circRNA expression profile in human epicardial adipose tissue (EAT) remains undefined. RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease (CAD) cases between the heart failure (HF) and non-HF groups. The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response, including KIAA0182, RHOBTB3, HIPK3, UBXN7, PCMTD1, N4BP2L2, CFLAR, EPB41L2, FCHO2, FNDC3B and SPECC1. Among the 141 circRNAs substantially different between the HF and non-HF groups (P<0.05;fold change>2), hsa_circ_0005565 stood out, and was mostly associated with positive regulation of metabolic processes and insulin resistancein GO and KEGG pathway analyses, respectively. These data indicate EAT circRNAs contribute to the pathogenesis of metabolic disorders causing HF.

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 Circular RNA Expression Profiles in Plasma from Patients with Heart Failure Related to Platelet Activity

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 187 ◽  
Author(s):  
Yeying Sun ◽  
Xiaoli Jiang ◽  
Yan Lv ◽  
Xinyue Liang ◽  
Bingrui Zhao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Expression Profiles ◽  
Roc Curves ◽  
Serum Levels ◽  
Circular Rna ◽  
Diagnostic Value ◽  
Circular Rnas ◽  
Healthy Controls ◽  
Platelet Activity ◽  
Pathway Analyses

Heart failure (HF) is a deadly disease that is difficult to accurately diagnose. Circular RNAs (circRNAs) are a novel class of noncoding RNAs that might play important roles in many cardiovascular diseases. However, their role in HF remains unclear. CircRNA microarrays were performed on plasma samples obtained from three patients with HF and three healthy controls. The profiling results were validated by quantitative reverse transcription polymerase chain reaction. The diagnostic value of circRNAs for HF was evaluated by receiver operating characteristic (ROC) curves. The expression profiles indicated that 477 circRNAs were upregulated and 219 were downregulated in the plasma of patients with HF compared with healthy controls. Among the dysregulated circRNAs, hsa_circ_0112085 (p = 0.0032), hsa_circ_0062960 (p = 0.0006), hsa_circ_0053919 (p = 0.0074) and hsa_circ_0014010 (p = 0.025) showed significantly higher expression in patients with HF compared with healthy controls. The area under the ROC curve for hsa_circ_0062960 for HF diagnosis was 0.838 (p < 0.0001). Correlation analysis showed that the expression of hsa_circ_0062960 was highly correlated with B-type natriuretic peptide (BNP) serum levels. Some differential circRNAs were found to be related to platelet activity by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The landscape of circRNA expression profiles may play a role in HF pathogenesis and improve our understanding of platelet function in HF. Moreover, hsa_circ_0062960 has potential as a novel diagnostic biomarker for HF.

scholarly journals Expression profiles of circular RNA in granulosa cells from women with biochemical premature ovarian insufficiency

Epigenomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 319-332
Author(s):  
Xing-Yu Zhou ◽  
Ying Li ◽  
Jun Zhang ◽  
Yu-Dong Liu ◽  
Jing Zhe ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Granulosa Cells ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Circular Rna ◽  
Premature Ovarian Insufficiency ◽  
Circular Rnas ◽  
Ovarian Insufficiency ◽  
Paired Samples ◽  
Foxo Signaling Pathway

Aim: To identify the expression profiles and potential functions of circular RNAs (circRNAs) in granulosa cells (GCs) from women with biochemical premature ovarian insufficiency (bPOI). Patients & methods: CircRNAs microarray analysis was performed to GCs from 8 patients with bPOI and 8 control women, followed by qRT-PCR in 15 paired samples. CircRNA–miRNA networks and the prediction of their enriched signaling pathways were conducted by bioinformatics analysis. Results: A total of 133 upregulated and 424 downregulated circRNAs was identified in women with bPOI. We constructed circRNA–miRNA networks and found that the most predominantly enriched signaling pathways were the FoxO signaling pathway and cellular senescence. Conclusion: CircRNAs are differentially expressed in bPOI, which might contribute to the pathogenesis of bPOI.

scholarly journals The functions and clinical significance of circRNAs in hematological malignancies

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiangxiang Zhou ◽  
Linquan Zhan ◽  
Kai Huang ◽  
Xin Wang
Keyword(s):  
Molecular Mechanisms ◽  
Hematological Malignancies ◽  
Clinical Applications ◽  
Mrna Splicing ◽  
Circular Rnas ◽  
Biological Processes ◽  
The Novel ◽  
Novel Biomarkers ◽  
Regulatory Rnas ◽  
By Products

Abstract With covalently closed circular structures, circular RNAs (circRNAs) were once misinterpreted as by-products of mRNA splicing. Being abundant, stable, highly conserved, and tissue-specific, circRNAs are recently identified as a type of regulatory RNAs. CircRNAs bind to certain miRNAs or proteins to participate in gene transcription and translation. Emerging evidence has indicated that the dysregulation of circRNAs is closely linked to the tumorigenesis and treatment response of hematological malignancies. CircRNAs play critical roles in various biological processes, including tumorigenesis, drug resistance, tumor metabolism, autophagy, pyroptosis, and ferroptosis. The N6-methyladenosine modification of circRNAs and discovery of fusion-circRNAs provide novel insights into the functions of circRNAs. Targeting circRNAs in hematological malignancies will be an attractive treatment strategy. In this review, we systematically summarize recent advances toward the novel functions and molecular mechanisms of circRNAs in hematological malignancies, and highlight the potential clinical applications of circRNAs as novel biomarkers and therapeutic targets for future exploration.

scholarly journals Differential circular RNA expression profiles in umbilical cord blood exosomes from preeclampsia patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Minkai Cao ◽  
Juan Wen ◽  
Chaozhi Bu ◽  
Chunyan Li ◽  
Yu Lin ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Expression Profiles ◽  
Circular Rna ◽  
Circular Rnas ◽  
Pathway Network ◽  
Pathway Analyses ◽  
Normal Controls

Abstract Background Exosomal circular RNAs (circRNAs) are emerging as important regulators of physiological development and disease pathogenesis. However, the roles of exosomal circRNAs from umbilical cord blood in preeclampsia (PE) occurrence remains poorly understood. Methods We used microarray technology to establish the differential circRNA expression profiles in umbilical cord blood exosomes from PE patients compared with normal controls. Bioinformatics analysis was conducted to further predict the potential effects of the differentially expressed circRNAs and their interactions with miRNAs. Results According to the microarray data, we identified 143 significantly up-regulated circRNAs and 161 significantly down-regulated circRNAs in umbilical cord blood exosomes of PE patients compared with controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses showed that circRNA parental genes involved in the regulation of metabolic process, trophoblast growth and invasion were significantly enriched, which play important roles in PE development. Moreover, pathway network was constructed to reveal the key pathways in PE, such as PI3K-Akt signaling pathway. Further circRNA/miRNA interactions analysis demonstrated that most exosomal circRNAs had miRNA binding sites, and some miRNAs were associated with PE. Conclusions Our results highlight the importance of exosomal circRNAs in the pathogenesis of PE and lay a foundation for extensive studies on the role of exosomal circRNAs in PE development.

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.

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