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 ◽  
...  

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.

2019 ◽  
Author(s):  
Meili Zheng ◽  
Lei Zhao ◽  
Xinchun Yang

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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Minkai Cao ◽  
Juan Wen ◽  
Chaozhi Bu ◽  
Chunyan Li ◽  
Yu Lin ◽  
...  

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.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dao-xiong Ye ◽  
Si-si Wang ◽  
Ying Huang ◽  
Pan Chi

Abstract Background Circular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and progression of cancer. Emerging studies also shows that circRNAs may function as potential markers for cancer diagnosis and treatment. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed. Methods CircRNA microarray was performed to detect the differentially expressed circRNAs in eight plasma samples, including four colorectal cancer (CRC) and four normal samples. Besides, the results of microarray were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, ROC curve evaluation was performed to calculate the diagnostic value of significantly dysregulated circRNAs. In order to predict the potential mechanism of the significant circRNAs, circRNA–miRNA–mRNA network was constructed based on the TargetScan, miRTarBase and MIRDB database, as well as CircInteractome online software. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to further predict the function of meaningful circRNAs. Results Totally three differentially expressed circRNAs were identified in CRC plasma compared to normal plasma by circRNA microarray analysis, and the results was validated by qRT-PCR. Hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445 were identified and ROC curves analysis was used to calculate the single and joint diagnostic value. Furthermore, GO and KEGG analyses revealed that functions were mainly cancer-related, which indicated that the circRNAs were meaningfully associated with CRC cell proliferation and metastasis. Conclusion In conclusion, we have identified three circRNAs that are dysregulated in CRC plasma, including hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445. ROC curves showed that these circRNAs might have diagnostic value for colorectal cancer. Furthermore, bioinformatics analysis indicated that the above-mentioned circRNAs might be involved in the development of CRC.


2020 ◽  
Author(s):  
Qi Li ◽  
Zhongjie Yu ◽  
Mengyang Li ◽  
Zhe Su ◽  
Yuanyong Wang ◽  
...  

Abstract Background: Myocardial infarction (MI) is one of the most widespread illnesses seriously harmful to human health. However, the mechanisms of its pathogenesis have not yet been completely proved. circRNA is one kind of non-coding RNA, recently published data suggests that circRNAs play a crucial role in heart diseases, but their expression profiles and role in MI patients are not yet completely defined. Methods: RNAs from peripheral blood samples were recruited for high-throughput RNA-seq analysis; The junction site part of circRNAs was confirmed by PCR with divergent primers; ROC curves were created to estimate the diagnostic value of circRNAs for MI; The expression level of circRNAs in clinical and cell samples were detected by RT-qPCR; MiRNA target site in exons of circRNA loci was verified by using miRanda, The binding sites of miRNA and mRNA were predicted by RNAhybrid; The regulatory roles of circSLC8A1 in cardiomyocytes were detected by TUNEL and Immunoblotting.Results: A total of 3862 circRNAs were detected to be remarkably changed, including 2738 circRNAs being upregulated, 1124 circRNAs being downregulated. circTMEM165, circUBAC2, circZNF609, circANKRD12, and circSLC8A1 were upregulated in MI and had closed loop structure. The results of ROC curves revealed that these five circRNAs had good sensitivity and specificity for MI diagnosis. Moreover, we created networks among circRNAs, miRNAs and mRNAs to predict the regulatory roles of circRNAs in MI. Besides that, we also demonstrated that circSLC8A1 contributed to cardiomyocytes apoptosis. Conclusions: In this study, we depicted the expression profiles of circular RNA in peripheral blood of myocardial infarction patients, revealed the five circRNAs may be very beneficial for MI diagnosis and regarded as possible biomarkers. Moreover, we also revealed that circSLC8A1 played a critical role in cardiomyocytes apoptosis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fan Yang ◽  
Xiaoli Fan ◽  
Yifeng Liu ◽  
Yi Shen ◽  
Shenglan Zhao ◽  
...  

Autoimmune hepatitis (AIH) is a chronic liver disease caused by disruption of liver immune homeostasis. The effect of dendritic cells (DCs) on the pathogenesis of AIH is not fully understood. Long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) have been shown to play critical roles in the regulation of cell function. In this study, we analyzed the immunophenotypic characteristics of DCs in the peripheral blood. The percentage of mature DCs was higher in AIH patients than in healthy controls (HCs), and the proportion of mature DCs decreased after treatment. We isolated monocyte-derived DCs (moDCs) from the peripheral blood, obtained whole RNA-sequencing (RNA-seq) data for the moDCs from the two groups, and identified differentially expressed (DE) lncRNAs, circRNAs, miRNAs and mRNAs. In addition, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for the DE mRNAs and constructed competing endogenous RNA (ceRNA) networks. ENST00000543334, hsa_circ_0000279, and hsa_circ_0005076 were selected and validated by RT-qPCR. These results provide a possible molecular mechanism of DCs in the pathogenesis of AIH and identify some potential therapeutic targets.


2021 ◽  
Author(s):  
Minkai Cao ◽  
Juan Wen ◽  
Chaozhi Bu ◽  
Chunyan Li ◽  
Yu Lin ◽  
...  

Abstract 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. In this study, we used microarray technology to establish the differential circRNA expression profiles in umbilical cord blood exosomes from PE patients compared with normal controls. 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 demonstrated that circRNA parental genes involved in the regulation of metabolic process, trophoblast growth and invasion were significantly enriched, which are important 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 showed that most of the exosomal circRNAs harbored miRNA binding sites, and some miRNAs were associated with PE. Collectively, 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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aijun Sun ◽  
Rui Wang ◽  
Shuaikang Yang ◽  
Xiaojing Zhu ◽  
Ying Liu ◽  
...  

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.


Author(s):  
Han-Wen Chen ◽  
Xiao-Xia Zhang ◽  
Zhu-Ding Peng ◽  
Zu-Min Xing ◽  
Yi-Wen Zhang ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fangzheng Shang ◽  
Yu Wang ◽  
Rong Ma ◽  
Zhengyang Di ◽  
Zhihong Wu ◽  
...  

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.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Melika Ameli-Mojarad ◽  
Mandana Ameli-Mojarad ◽  
Mitra Nourbakhsh ◽  
Ehsan Nazemalhosseini-Mojarad

Breast cancer (BC) is one of the most common lethal diseases in women worldwide. Recent evidence has shown that covalently closed Circular RNA (circRNA) deregulation is observed in different human malignancies and cancers. Lately, circRNAs are being considered as a new diagnostic biomarker; however, the mechanism and the correlation of action between circRNAs and BC are still unclear. In the present study, we try to investigate the expression level of hsa_circ_0005046 and hsa_circ_0001791 in BC. By using quantitative real-time polymerase chain reaction (qRT-PCR), expression profiles of candidate circRNAs were detected in 60 BC tissue and paired adjacent normal tissues. Furthermore, the clinicopathological relation and diagnostic value were estimated. Our results showed the higher expression levels of hsa_circ_0005046 and hsa_circ_0001791 in BC tissues compared to paired adjacent normal tissues with P value ( P < 0.0001 ) for both circRNAs, and the area under the receiver operating characteristic (ROC) curve was 0.857 and 1.0, respectively; in addition, a total 10 miRNAs that can be targeted by each candidate circRNAs was predicted base on bioinformatics databases. Taken together, for the first time, the results of our study presented high expression levels of hsa_circ_0005046 and hsa_circ_00017916 in BC; although there was no direct correlation between the high expression level of both circRNAs with clinic pathological factors, except hsa_circ_0001791 association with estrogen receptors (ER), high ROC curve in expressed samples indicated that both circRNAs could be used as a new diagnostic biomarker for BC. Moreover, miRNAs selection tools predicted that miR-215 and mir-383-5p which have a tumor suppressor role in BC can be targeted by our candidate circRNAs to affect the PI3K/AKT pathway; in conclusion, further studies are required to validate the oncogene role of our candidate circRNAs through the PI3k pathway.


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