RNA-sequencing of peripheral blood circular RNAs in Parkinson disease.
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ABSTRACT: Background
Circular RNAs (circRNAs) play an important role in many neurological diseases and can serve as biomarkers for these diseases. However, the information about circRNAs in Parkinson disease (PD) remained limited. In this study, we aimed to determine the circRNAs expression profile in PD patients and discuss the significance of circRNAs in the diagnosis of PD.Methods and results
Using RNA-sequencing in peripheral blood RNAs, we showed that a significant number of mRNAs or circRNAs were differentially expressed between PD patients and normal controls (NCs), which included 273 up-regulated and 493 down-regulated mRNAs, and 129 up-regulated and 282 down-regulated circRNAs, respectively. Functional analysis was performed using the Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis, and the results showed that the second most enriched KEGG pathway was PD. These data suggest that the levels of mRNAs and circRNAs in peripheral blood could be potentially used as biomarkers for PD. In addition, we correlated mRNAs and circRNAs by constructing a competing endogenous RNA (ceRNA) network in PD. The resulted-in ceRNA network included 10 differentially expressed mRNAs from PD pathway, 13 predicted miRNAs, and 10 differentially expressed circRNAs.Conclusion
Collectively, we first characterized the expression profiles of circRNAs and mRNAs in peripheral blood from PD patients and proposed their possible characters in the pathogenesis of PD. These results provided valuable insights into the clues underlying the pathogenesis of PD.
SUBMITTER: Kong F
PROVIDER: S-EPMC8202568 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNew noninvasive and affordable molecular approaches that will complement current practices and increase the accuracy of Parkinson's disease (PD) diagnosis are urgently needed. Circular RNAs (circRNAs) are stable noncoding RNAs that accumulate with aging in neurons and are increasingly shown to regulate all aspects of neuronal development and function.ObjectivesΤhe aims of this study were to identify differentially expressed circRNAs in blood mononuclear cells of patients with idiopathic PD and explore the competing endogenous RNA networks affected.MethodsEighty-seven circRNAs were initially selected based on relatively high gene expression in the human brain. More than half of these were readily detectable in blood mononuclear cells using real-time reverse transcription-polymerase chain reaction. Comparative expression analysis was then performed in blood mononuclear cells from 60 control subjects and 60 idiopathic subjects with PD.ResultsSix circRNAs were significantly down-regulated in patients with PD. The classifier that best distinguished PD consisted of four circRNAs with an area under the curve of 0.84. Cross-linking immunoprecipitation-sequencing data revealed that the RNA-binding proteins bound by most of the deregulated circRNAs include the neurodegeneration-associated FUS, TDP43, FMR1, and ATXN2. MicroRNAs predicted to be sequestered by most deregulated circRNAs have the Gene Ontology categories "protein modification" and "transcription factor activity" mostly enriched.ConclusionsThis is the first study that identifies specific circRNAs that may serve as diagnostic biomarkers for PD. Because they are highly expressed in the brain and are derived from genes with essential brain functions, they may also hint on the PD pathways affected. © 2021 Biomedical Research Foundation, Academy of Athens. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
| S-EPMC8248110 | biostudies-literature
Project description:BackgroundCircular RNA (circRNA) is a type of closed circular noncoding RNA (ncRNA), mostly formed by back-splicing or alternative splicing of pre-messenger RNA (mRNA). The aim of this study was to explore the expression profile of circRNA in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and discover potential molecular markers of AS.MethodsThe circRNA microarray technology was used to detect the expression of circRNAs in the peripheral blood of 6 patients with AS and 6 healthy controls (HC). To screen the differentially expressed circRNAs by fold change (FC) and P value, these differentially expressed circRNAs were analyzed by bioinformatics. In 60 cases of AS and 30 cases of HC, 4 circRNAs were subjected to real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and their correlation with various clinical indicators was analyzed. Finally, the receiver operating characteristic (ROC) curve was used to analyze their potential as AS diagnostic markers.ResultsThe microarray results showed that there were 1369 significantly differently expressed (P < 0.05, FC > 1.5) circRNAs between the AS and HC groups (675 upregulated and 694 downregulated). The results of bioinformatics analysis suggested that they were mainly involved in "enzyme binding," "adenosine ribonucleotide binding," "MAPK signaling pathway", etc. The RT-qPCR results showed that the expressions of hsa_circRNA_001544 (U = 486.5, P < 0.05) and hsa_circRNA_102532 (U = 645, P < 0.05) were significantly different between the AS group and the HC group. The AS group was further divided into two subgroups: active AS (ASA) and stable AS (ASS). After analysis, it was found that compared with the HC group, hsa_circRNA_001544 was significantly increased in both ASA (U = 214, P < 0.05) and ASS groups (U = 273, P < 0.05), while hsa_circRNA_008961 (U = 250, P < 0.05) and hsa_circRNA_102532 (U = 295, P < 0.05) were only significantly increased in the ASA group. Furthermore, hsa_circRNA_012732 was significantly different between the ASA and ASS groups (U = 194, P < 0.05), and there was no statistical significance among the remaining groups. Correlation analysis results showed that hsa_circRNA_012732 was negatively correlated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), high-sensitivity C-reactive protein (hsCRP), and globulin (GLOB) and positively correlated with lymphocyte count (LY), mean corpusular volume, and albumin (ALB), and hsa_circRNA_008961 was negatively correlated with platelet (PLT) count. ROC curve analysis showed that hsa_circRNA_001544 (95% CI = 0.610-0.831, P < 0.05) and hsa_circRNA_102532 (95% CI = 0.521-0.762, P < 0.05) were statistically significant, and their area under curve (AUC) values were 0.720 and 0.642, respectively.ConclusionsThere are differentially expressed circRNAs in PBMCs of AS patients, and they may be involved in the occurrence and development of AS. Among these differentially expressed circRNAs, hsa_circRNA_012732 has the potential to become an indicator of disease activity, and hsa_circRNA_001544 has the potential to become a molecular marker for AS diagnosis.
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Project description:Circular RNAs (circRNAs) have recently been discovered as a novel type of endogenous non-coding RNA that may regulate gene expression in mammals. In the central nervous system (CNS), circRNAs are relevant to many neurological disorders such as Alzheimer's disease (AD). In this study, we attempted to identify an aberrant circRNA, hsa_circ_0003391, which is significantly downregulated in the peripheral blood of patients with AD, and to explore the relationship between hsa_circ_0003391 and the clinical manifestation of AD. The expression of hsa_circ_0003391 had a specific decrease in the peripheral blood of patients with AD compared to those with other types of dementia. To evaluate the potential diagnostic value of the circRNA, we performed a receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) value was 0.7283 for hsa_circ_0003391, which was statistically significant. The natural form of hsa_circ_0003391 in the peripheral blood was a loop structure with good stability. We found a potential correlation between the expression of hsa_circ_0003391 and the clinical manifestations of AD. Bioinformatic analysis was carried out to predict the latent target microRNAs (miRNA) of hsa_circ_0003391. Furthermore, microRNAs targeted by hsa_circ_0003391 were successfully detected, and miR-574-5p had an expected elevation in the AD groups, suggesting that miR-574-5p might be a potential microRNA target for hsa_circ_0003391. Our results suggest that the downregulation of hsa_circ_0003391 in the peripheral blood has a potential relationship with AD. Our findings not only provide an important latent biomarker but also highlight an important perspective for the following study into AD pathogenesis. This may promote the process of novel therapeutics targeting non-coding RNA.
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Project description:Circular RNAs (circRNAs) are a new class of RNAs that can be used as biomarkers in clinical blood samples. However, little is known about circRNAs' diagnostic values for rheumatoid arthritis (RA). In this study, the hsa_circ_0054189, hsa_circ_0008675, hsa_circ_0082689, hsa_circ_0082688, hsa_circ_0010932, hsa_circ_0002473 and hsa_circ_0044235 in peripheral blood were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). For hsa_circ_0044235, only one abnormal expression circRNAs in peripheral blood was selected as a targeted circRNA to explore the diagnostic value for RA. Our work demonstrated that the hsa_circ_0044235 in peripheral blood was decreased significantly in RA patients. The hsa_circ_0044235 in peripheral blood from RA patients did not correlate with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) or disease activity score 28 (DAS28). Receiver operating characteristic (ROC) curve analysis suggested that the hsa_circ_0044235 in peripheral blood has significant value in the diagnosis of RA. The risk score based on hsa_circ_0044235 in peripheral blood also distinguished significantly the patients with RA from systemic lupus erythematosus (SLE). This study suggests that the hsa_circ_0044235 in peripheral blood may be a potential biomarker of patients with RA.
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Project description:Circular RNAs (circRNAs) are a novel class of RNAs with closed loop structure. Blood circRNAs are widely acknowledged to be more stable than linear mRNAs, which show promising prospect to be liquid biopsy biomarkers for clinical applications. However, accumulating studies have demonstrated that sample processing delays have profound effects on blood transcriptome expression profiles, wherein knowledge remains elusive about the impacts of prolonged sample processing on blood expression profiles of circRNAs. We collected whole blood samples from three donors and isolated peripheral blood mononuclear cells (PBMCs) at six different incubation time points. We measured total RNA expression profiles using RNA sequencing (RNA-seq) and investigated the differentially expressed circRNAs, mRNAs and lncRNAs upon blood processing delay. Meanwhile, we explored the underlying inducement of aberrant expression of circRNAs against their corresponding mRNA transcripts. Finally, we utilized rMATS-turbo and CIRI-AS, respectively, to screen out differential alternative splicing (AS) events in linear mRNAs and circRNAs. Sample incubation at 4°C lasting to 48 hours (h) led to minimal effects to circRNAs' expression. However, it induced extensive alterations for mRNAs and lncRNAs when the incubation time was beyond 12 h. Additionally, only 2 h processing delays may result in profound impacts on AS events of linear mRNAs, while less impact on the equivalence of circRNAs. Our results suggested that PBMC circRNAs are stable upon sample processing delay, which are more suitable to be liquid biopsy biomarkers.
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Project description:BackgroundCircular RNAs (circRNAs) are emerging noncoding RNAs that are involved in many biological processes and diseases. The expression profile of circRNAs in preterm neonates with bronchopulmonary dysplasia (BPD) remains unresolved.MethodsIn BPD infants, peripheral venous blood was drawn and circRNAs were extracted and sequenced by next-generation sequencing. The levels of the selected circRNAs were measured by real-time quantitative reverse transcription PCR.ResultsAmong thousands of circRNAs, 491 circRNAs were significantly changed. Among the top 10 changed circRNAs, hsa_circ_0003122, hsa_circ_0003357, hsa_circ_0009983, hsa_circ_0003037, and hsa_circ_0009256 were significantly increased, while hsa_circ_0014932, hsa_circ_0015109, hsa_circ_0017811, hsa_circ_0020588, and hsa_circ_0015066 were significantly decreased. These altered circRNAs are involved in complicated biological functions and signaling pathways. Additionally, hsa_circ_0005577 (hsa_circ_FANCL), which was significantly increased in the moderate-to-severe BPD subjects, was correlated with oxygenation therapy.ConclusionThese results suggest that an aberrant circRNA profile in the peripheral blood of BPD infants might be important in BPD pathogenesis.
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Project description:The aim of the present study was to investigate the expression of circular RNAs (circRNAs) in the peripheral blood of coronary artery disease (CAD) patients and the potential use of circRNAs as diagnostic biomarkers of CAD. We first analysed peripheral blood circRNAs of 12 CAD patients and 12 control individuals by RNA microarray and found that 22 circRNAs were differentially expressed between these two groups: 12 were upregulated, and 10 were downregulated. Then, we selected 5 circRNAs as candidate biomarkers under stricter screening criteria and verified them in another group of subjects consisting of 30 control individuals and 30 CAD patients with different SYNTAX scores. These 5 circRNAs were all remarkably increased in the CAD group. Hsa_circ_0124644 had the largest area under the curve (AUC). We tested hsa_circ_0124644 in an independent cohort consisting of 115 control individuals and 137 CAD patients. After we included the risk factors for CAD, the AUC slightly increased from 0.769 (95% confidence interval?=?[0.710-0.827], P?<?0.001) to 0.804 ([0.751-0.857], P?<?0.001), and when combined with hsa_circ_0098964, the diagnostic value slightly increased. Taken together, our results suggest that hsa_circ_0124644 can be used as a diagnostic biomarker of CAD.
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Project description:The study was to characterize the expression profiles of circular RNAs (circRNAs) in peripheral blood mononuclear cells (PBMCs) from active tuberculosis (TB) patients and to investigate their function. Microarray was applied to detect circRNA expression and reverse transcription-quantitative polymerase chain reaction was conducted to validate the microarray results. Meanwhile, receiver operating characteristic curve (ROC) curve was calculated to evaluate the predictive power of the selected circRNAs for TB diagnosis. Additionally, circRNA/miRNA interaction was predicted based on miRNA target prediction software, and gene ontology as well as Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to predict their biological function. In total, 171 circRNAs were found to be dysregulated in TB samples. Specifically, circRNA_103017, circRNA_059914 and circRNA_101128 were confirmed to be increased, while circRNA_062400 was decreased in TB samples. ROC analysis revealed that circRNA_103017 had potential value for TB diagnosis, followed by circRNA_059914 and circRNA_101128. Moreover, circRNA_101128 expression in TB samples was negatively correlated with the level of its possible target let-7a and bioinformatics analysis showed that circRNA_101128 was potentially involved in MAPK and P13K-Akt pathway possibly via modulation of let-7a. Taken together, our results indicated that some dysregulated circRNAs were potential biomarkers for the diagnosis of TB and circRNA_101128-let-7a interplay may play considerable role in PBMCs response to Mtb infection.
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Project description:Circular RNAs (circRNAs) are a class of non-coding RNAs that participate in various biological processes. However, the function of circRNAs in neonatal hypoxic‑ischemic encephalopathy (HIE) is not fully understood. In the present study, the differentially expressed circRNAs in the peripheral blood of neonates with HIE and control samples were characterized by a microarray assay. A total of 456 circRNAs were significantly differentially expressed in the peripheral blood of neonates with HIE, with 250 upregulated and 206 downregulated circRNAs in HIE compared with the control samples. Reverse transcription‑quantitative PCR was used to investigate specific circRNAs. Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to determine the function of the parent genes of the dysregulated circRNAs. In addition, microRNAs that may be associated with specific circRNAs were predicted using miRanda. Collectively, the present results indicated the potential importance of circRNAs in the peripheral blood of neonates with HIE.
| S-EPMC7248490 | biostudies-literature
Project description:BackgroundCircular RNA (circRNA), a class of RNA molecule with a loop structure, has recently attracted researchers due to its diverse biological functions and potential biomarkers of human diseases. Most of the current circRNA detection methods from RNA-sequencing (RNA-Seq) data utilize the mapping information of paired-end (PE) reads to eliminate false positives. However, much of the practical RNA-Seq data such as cross-linking immunoprecipitation sequencing (CLIP-Seq) data usually contain single-end (SE) reads. It is not clear how well these tools perform on SE RNA-Seq data.ResultsIn this study, we present a systematic evaluation of six advanced RNA-based methods and two CLIP-Seq based methods for detecting circRNAs from SE RNA-Seq data. The performances of the methods are rigorously assessed based on precision, sensitivity, F1 score, and true discovery rate. We investigate the impacts of read length, false positive ratio, sequencing depth and PE mapping information on the performances of the methods using simulated SE RNA-Seq simulated datasets. The real datasets used in this study consist of four experimental RNA-Seq datasets with ≥100bp read length and 124 CLIP-Seq samples from 45 studies that contain mostly short-read (≤50bp) RNA-Seq data. The simulation study shows that the sensitivities of most of the methods can be improved by increasing either read length or sequencing depth, and that the levels of false positive rates significantly affect the precision of all methods. Furthermore, the PE mapping information can improve the method's precision but can not always guarantee the increase of F1 score. Overall, no method is dominant for all SE RNA-Seq data. The RNA-based methods perform better for the long-read datasets but are worse for the short-read datasets. In contrast, the CLIP-Seq based methods outperform the RNA-Seq based methods for all the short-read samples. Combining the results of these methods can significantly improve precision in the CLIP-Seq data.ConclusionsThe results provide a systematic evaluation of circRNA detection methods on SE RNA-Seq data that would facilitate researchers' strategies in circRNA analysis.
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