Circular RNA expression profiles in the plasma of patients with infantile hemangioma determined using microarray analysis
Ontology highlight
ABSTRACT: This study compared the circRNA expression levels in plasma samples from patients with IH and control individuals. The circRNA expression profiles were determined using microarray in three pairs of plasma samples from patients with proliferative IH and healthy control individuals. Expression of the identified circRNAs was verified using quantitative reverse transcription polymerase chain reaction (RT-qPCR), and bioinformatic analysis was performed to predict the microRNAs targeted by the validated circRNAs. In the circRNA expression profiles in the plasma of patients with IHs, we found 128 differentially expressed circRNAs, of which 72 were upregulated and 56 were downregulated. The downregulated expression of three circRNAs (hsa_circRNA_101566, hsa_circRNA_103546, and hsa_circRNA_103573) was verified using RT-qPCR. Circular RNAs (circRNAs) are noncoding RNAs that play important roles in tumor progression. Few studies have examined the circRNAs involved in infantile hemangioma (IH) progression. This study compared the circRNA expression levels in plasma samples from patients with IH and control individuals. The circRNA expression profiles were determined using microarray in three pairs of plasma samples from patients with proliferative IH and healthy control individuals. Expression of the identified circRNAs was verified using quantitative reverse transcription polymerase chain reaction (RT-qPCR), and bioinformatic analysis was performed to predict the microRNAs targeted by the validated circRNAs. In the circRNA expression profiles in the plasma of patients with IHs, we found 128 differentially expressed circRNAs, of which 72 were upregulated and 56 were downregulated. The downregulated expression of three circRNAs (hsa_circRNA_101566, hsa_circRNA_103546, and hsa_circRNA_103573) was verified using RT-qPCR. Gene ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that all identified networks participated in angiogenesis and tumor formation and progression. We found that hsa_circRNA_101566, which can regulate the mammalian target of rapamycin signaling pathway, may be an important regulatory molecule in IH development and that targeting of hsa_miR_520c can indirectly regulate the vascular endothelial growth factor signaling pathway. Further studies are needed to clarify these effects and the underlying mechanisms.
Project description:This study investigated the pathogenesis of Alzheimer’s disease by analyzing the differential expression of circular RNAs (circRNAs), and their interactions with microRNAs (miRNAs). A circRNA microarray was used to screen expressed circRNAs in peripheral blood leukocytes from three patients with AD and four healthy control participants. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to annotate the functions of the circRNAs. Changes in expression of six circRNAs [0045808/0070162/0001929/0092270/0092222/0092223]) was confirmed by RT-qPCR, of which three (hsa_circ_[0045808/0070162/0092270]) were further verified by RT-qPCR using a large sample of 23 patients with AD and 25 healthy controls. A circRNA-miRNA-mRNA interaction network, constructed using TargetScan, miRanda, and Cytoscape, revealed upregulated (n=311) and downregulated (n=433) circRNAs, whereaswhile 443 circRNAs were downregulated. GO and KEGG analyses associated differentially expressed circRNAs to neurotransmitters, cell senescence, P53, mTOR, and PI3K-AKT. Microarray sample verification using RT-qPCR confirmed the microarray analysis results on changes in the six circRNAs. Contrary to the microarray analysis, large-sample verification of significantly elevated circRNA expression was partially consistent (hsa_circ_0092270), and inconsistent (hsa_circ_0045808, hsa_circ_0070162), with the microarray results. The findings highlight the significance of circRNAs in AD and that hsa_circ_0092270 represents a promising biomarker for future studies.
Project description:Objective: Bladder outlet obstruction (BOO) is a common urologic disease associated with poorly understood molecular mechanisms. This study aimed to investigate the possible involvements of circRNAs (circular RNAs) and circRNA-encoded proteins in BOO development. Methods: The rat BOO model was established by the partial bladder outlet obstruction surgery. Differential expression of circRNA and protein profiles were characterized by deep RNA sequencing and iTRAQ quantitative proteomics respectively. Novel proteins encoded by circRNAs were predicted through ORF (open reading frame) selection using the GETORF software and verified by the mass spectrometry in proteomics, combined with the validation of their expressional alterations by quantitative RT-PCR. Results: Totally 3051 circRNAs were differentially expressed in bladder tissues of rat BOO model with widespread genomic distributions, including 1414 up-regulated and 1637 down-regulated circRNAs. Our following quantitative proteomics revealed significant changes of 85 proteins in rat BOO model, which were enriched in multiple biological processes and signaling pathways such as the PPAR and Wnt pathways. Among them, 21 differentially expressed proteins were predicted to be encoded by circRNAs and showed consistent circRNA and protein levels in rat BOO model. The expression of five protein-encoding circRNA were further validated by quantitative RT-PCR and mass spectrometry. Conclusion: The circRNA and protein profiles were substantially altered in rat BOO model, with great expressional changes of circRNA-encoded novel proteins.
Project description:Background: Circular RNA (circRNA) has been reported to be involved in the pathogenesis of cardiovascular disease (CVD), however, it is unclear whether circRNA carried by exosomes (exos) can be used as biomarkers for chronic coronary syndrome (CCS). This study aimed to investigate the expression pattern of exosomal circRNAs in the plasma of CCS patients, and to screen exo-circRNAs that can act as biomarkers for the diagnosis of CCS. Methods: High-throughput sequencing technology was carried out in the plasma exosomal RNA of 15 CCS patients and 15 non-cardiac chest pain patients (NCCP, control group) (sequencing cohort) to screen for differentially expressed circRNAs. Selected differentially expressed exo-circRNAs were further verified by real time polymerase chain reaction (RT-PCR) in a small-sample cohort (derivation cohort) and a large-sample cohort (validation cohort). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of exo-circRNAs for CCS patients. Results: By high-throughput sequencing of circRNAs in 15 CCS patients and 15 NCCP patients, 276 circRNAs differentially expressed in plasma exosomes of CCS patients were screened by using |log2(Fold change) |>1 and q-value<0.001, and 103 were up-regulated and 173 were down-regulated. Among the 103 up-regulated circRNAs, 5 circRNAs with high expression levels and significantly increased in plasma exosomes of CCS patients were selected for validation. Twice RT-PCR validation demonstrated that exo-hsa_circ_0075269 and exo-hsa_circ_0000284 were significantly up-regulated in patients with CCS (P<0.001). Circulating exo-hsa_circ_0075269 and exo-hsa_circ_0000284 yielded the area under the curve (AUC) values of 0.761 (P<0.001, 95%CI=0.669, 0.852) and 0.623 (P=0.015, 95%CI=0.522, 0.724) for CCS, respectively by ROC curve analysis. Moreover, AUC of hsa_circ_0075269 combined with hsa_circ_0000284 for diagnosing CCS was 0.741 (P<0.001, 95%CI=0.667, 0.850). Conclusion: The expression profile of circRNA in plasma exosomes of patients with CCS was significantly different from that of the control group. Plasma exo-hsa_circ_0075269 and exo-hsa_circ_0000284 have the potential to be new biomarkers for CCS diagnosis.
Project description:To determine the circRNA expression profile in IH and matched non-tumor tissues, we uesed circRNA microArray analysis form Arraystar to examine the expression of circRNAs in IH and matched non-tumor tissues.
Project description:Arraystar Human circRNA Microarray is designed for the global profiling of human circRNAs. In this study, we applied a circRNA microarray to screen the potential biomarker for HCC. 20 samples extracted from plasma samples including HCC group before operation, and after operation, CH group and control group. Each group contained five samples.
Project description:Exosomal circRNA sequencing was used to identify differentially expressed circRNAs between LAA stroke and normal controls. From a further validation stage, the results were validated using RT-qPCR.
Project description:In order to explore the role of circRNA in diabetic kidney disease (DKD), we employed circRNAs microarray expression profile in the plasma of daibetes patients (n=6), diabetic kidney disease patients (n=6) and healthy controls (n=6). According to the microarray data, we found 2079 differentially expressed circRNA in the plasma of DKD patients compared to the healthy people, including 1182 up-regulated and 897 down-regulated.Among the differentially expressed circRNA, nine DKD-related circRNAs were chosen and further validated by qRT-PCR.The results revealed that circUBXN7 was significantly elevated in the plasma of DKD patients, and might be a diagnostic plasma marker for DKD.
Project description:Circular RNAs (circRNAs) are a large class of animal RNAs. To investigate possible circRNA functions, it is important to understand circRNA biogenesis. Besides human Alu repeats, sequence features that promote exon circularization are largely unknown. We experimentally identified new circRNAs in C. elegans. Reverse complementary sequences between introns bracketing circRNAs were significantly enriched compared to linear controls. By scoring the presence of reverse complementary sequences in human introns we predicted and experimentally validated novel circRNAs. We show that introns bracketing circRNAs are highly enriched in RNA editing or hyper-editing events. Knockdown of the double-strand RNA editing ADAR1 enzyme significantly and specifically up-regulated circRNA expression. Together, our data support a model of animal circRNA biogenesis in which competing RNA:RNA interactions of introns form larger structures which promote circularization of embedded exons, while ADAR1 antagonizes circRNA expression by melting stems within these interactions. Thus, we assign a new function to ADAR1. Examination of 12 samples in different stages of C.elegans development.
Project description:Background: There is growing evidence that circular RNAs (circRNAs) play an important role in a variety of diseases, including erectile dysfunction (ED). Nevertheless, the role of circRNAs in cavernous nerve-damaging ED (CNI-ED) is unknown. Here, we aimed to discover new circRNAs, investigate their potential role in the pathogenesis of CNI-ED, and construct a circRNA-miRNA-mRNA network. Methods: Twelve male Sprague Dawley rats were randomly divided into bilateral cavernous nerve crush (BCNC) and control groups. Four weeks after surgery, the spongy smooth muscle tissue of the rat penis was sequenced using high-throughput full transcriptome sequencing. We analyzed the expression profiles of circRNAs, miRNAs, and mRNAs in the two groups. Twenty circRNAs with significantly different expressions were selected for real-time polymerase chain reaction (RT-qPCR). The circRNA-miRNA-mRNA network was established using Cytoscape. Gene ontology (GO)-term and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the edgeR package. Results: RNA transcriptome sequencing showed that 4,587 circRNAs, 762 miRNAs, and 21,661 mRNAs were dysregulated in the BCNC group. The top 20 differentially expressed circRNAs were further verified via RT-qPCR. The ceRNA network contained 23 circRNA-miRNA pairs and 227 miRNA-mRNA pairs, including ten circRNAs, six miRNAs, and 227 mRNAs. GO analysis suggested that these ten circRNAs could regulate various processes, such as oxidation-reduction processes, lipid metabolic processes, apoptotic processes, and proteolysis. Furthermore, KEGG analysis of mRNAs in the ceRNA network showed that they were involved in energy metabolism and communication between cells. A protein‐protein interaction network was constructed with the 227 mRNAs, and five hub genes (Ccna2, Cxcl10, Pld1, Mapk11, and Mboat2) were identified. In addition, Using circRNADb, we found 12 circRNAs with protein-coding potential, three of which were highly conserved in humans and rats. Our study revealed a potential link between circRNAs, miRNAs, and mRNAs in CNI-ED, suggesting that circRNAs may contribute to the occurrence of ED by regulating the cellular energy metabolism in CNI-ED.
Project description:Role of circRNAs in active tuberculosis (TB) remains unknown. The present study was aimed to determine plasma circRNA expression profile in active TB patients to identify potential biomarker by circRNA microarrays.