Differential Expression Profiles and Functional Prediction of Circular RNAs in Pediatric Dilated Cardiomyopathy

Circular RNAs (circRNAs) have emerged as essential regulators and biomarkers in various diseases. To assess the different expression levels of circRNAs in pediatric dilated cardiomyopathy (PDCM) and explore their biological and mechanistic significance, we used RNA microarrays to identify differentially expressed circRNAs between three children diagnosed with PDCM and three healthy age-matched volunteers. The biological function of circRNAs was assessed with a circRNA–microRNA (miRNA)–mRNA interaction network constructed from Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in 25 children with PDCM and 25 healthy volunteers. We identified 257 up-regulated (fold change ≤ 0.5, P < 0.05) and 899 down-regulated (fold change ≥2, P < 0.05) circRNAs in PDCM patients when compared to healthy volunteers. The qRT-PCR experiments confirmed has_circ_0067735 down-regulation (0.45-fold, P < 0.001), has_circ_0070186 up-regulation (2.82-fold, P < 0.001), and has_circ_0069972 down-regulation (0.50-fold, P < 0.05). A functional analysis of these differentially expressed circRNAs suggests that they are associated with hypertrophy, remodeling, fibrosis, and autoimmunity. CircRNAs have been implicated in PDCM through largely unknown mechanisms. Here we report differentially expressed circRNAs in PDCM patients that may illuminate the mechanistic roles in the etiology of PDCM that could serve as non-invasive diagnostic biomarkers.

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Differentially Expressed Circular RNAs in Stenosed Arteriovenous Fistula Tissues of Uremia Patients

10.21203/rs.3.rs-864648/v1 ◽

2021 ◽

Author(s):

Lili Lan ◽

Yu Liu ◽

Menglin Zou ◽

Yihang Xie ◽

Yiye Zhang ◽

...

Keyword(s):

High Throughput Sequencing ◽

Expression Profiles ◽

Interaction Network ◽

Differentially Expressed ◽

Circular Rnas ◽

Effective Management ◽

Rna Seq ◽

Qrt Pcr ◽

Vascular Stenosis ◽

Polymerase Chain

Abstract BackgroundArteriovenous fistula (AVF) is the most common renal replacement therapy for uremic patients. However, stenosis in AVF may lead to AVF failure, hence prevention and effective management of AVF failure is an issue to be addressed. circular RNAs (circRNAs) dysregulation may be pivotal for the development and progression of AVF stenosis. MethodsFour stenosed tissues from AVF outflow veins and four normal venous tissues without vascular stenosis were collected for RNA-sequencing (RNA-seq). The circRNAs expression profiles were identified by high-throughput sequencing, and the functions and pathways of differentially expressed (DE) circRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Gene Genomes (KEGG) enrichment analyses. Seven DE circRNAs were screened for quantitative real‐time polymerase chain reaction (qRT-PCR) validation. circRNA-miRNA interaction network was constructed. ResultsA total of 17,620 circRNA transcripts were examined by RNA-seq, and 208 DE circrRNAs were identified between AG and CG, of which 92 were upregulated and 116 were downregulated. The expression trend in the four selected circRNAs was validated by qRT-PCR, which was consistent with the RNA-seq results. Dysregulated circRNAs may be involved in stenosis by mediating focal adhesion kinase (FAK) pathway. ConclusionOur study revealed abnormal circRNA expression in stenosed tissues of the AVF outflow vein, which was functionally classified. The results indicated that DE circRNAs in the stenosed tissues of AVF and their related FAK pathway have potential to be targets for the prevention and treatment of AVF failure.

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The Differentially Expressed Circular RNAs in the Substantia Nigra and Corpus Striatum of Nrf2-Knockout Mice

Cellular Physiology and Biochemistry ◽

10.1159/000494478 ◽

2018 ◽

Vol 50 (3) ◽

pp. 936-951 ◽

Cited By ~ 6

Author(s):

Jun-Hui Yang ◽

Run-Jiao Zhang ◽

Jia-Jie Lin ◽

Ming-Chao Cao ◽

Qie Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Substantia Nigra ◽

Microarray Analysis ◽

Corpus Striatum ◽

Neuronal Damage ◽

Interaction Network ◽

Differentially Expressed ◽

Circular Rnas ◽

Related Factor ◽

Qrt Pcr

Background/Aims: The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a protective role in both acute neuronal damage and chronic neurodegeneration-related oxidative stress. Circular RNAs (circRNAs) are involved with various diseases in the central nervous system (CNS). This study aimed to identify the key circRNAs involved in Nrf2-neuroprotection against oxidative stress. Methods: The differentially expressed circRNAs (DEcircRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice were identified by microarray analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of selected DEcircRNAs in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice. Based on our previous microarray analysis of the differentially expressed mRNAs (DEmRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice, the DEcircRNA-miRNA-DEmRNA interaction network was constructed. Functional annotation of DEmRNAs that shared the same binding miRNAs with DEcircRNAs was performed using gene ontology (GO) and pathway analyses. Results: A total of 65 and 150 significant DEcircRNAs were obtained in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, respectively, and seventeen shared DEcircRNAs were found in both these two tissues. The qRT-PCR results were generally consistent with the microarray results. The DEcircRNA-miRNA-DEmRNA interaction network and pathway analysis indicated that mmu_circRNA_34132, mmu_circRNA_017077 and mmu-circRNA-015216 might be involved with Nrf2-mediated neuroprotection against oxidative stress. Mmu_circRNA_015216 and mmu_circRNA_017077 might play roles in the Nrf2-related transcriptional misregulation and Nrf2-mediated processes of rheumatoid arthritis, respectively. In addition to these two processes, mmu_circRNA_34132 may be a potential regulator of Nrf2-mediated protection for diabetes mellitus and Nrf2-mediated defence against ROS in hearts. Conclusion: In conclusion, our study identified the key DEcircRNAs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, which might provide new clues for further exploring the mechanism of Nrf2-mediated neuroprotection against oxidative stress and other Nrf2-mediated processes.

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Differential expression profiles and functional analysis of circular RNAs in children with fulminant myocarditis

Epigenomics ◽

10.2217/epi-2019-0101 ◽

2019 ◽

Vol 11 (10) ◽

pp. 1129-1141 ◽

Cited By ~ 5

Author(s):

Li Zhang ◽

Bo Han ◽

Jing Wang ◽

Qingqing Liu ◽

Yaru Kong ◽

...

Keyword(s):

Functional Analysis ◽

Healthy Volunteers ◽

Differential Expression ◽

Expression Profiles ◽

Interaction Network ◽

Fulminant Myocarditis ◽

Circular Rnas ◽

Biological Functions ◽

Microarray Experiments ◽

Network Building

Aim: To assess differential expression profiles of circular RNAs (circRNAs) and explore their possible functions in children with fulminant myocarditis. Materials & methods: circRNA microarray experiments were carried out for determining differential expression profiles of circRNAs in three children with fulminant myocarditis and three healthy volunteers. Functional analysis and circRNA–miRNA–mRNA interaction network building were conducted to study biological functions. Results: This work identified 2281 upregulated and 892 downregulated circRNAs. Further assessment confirmed hsa_circ_0071542 upregulation (2.5-fold) in fulminant myocarditis. Functional analysis demonstrated the differentially expressed circRNAs mainly contributed to inflammation and immunity. Conclusion: circRNAs might have substantial roles in pediatric fulminant myocarditis, and hsa_circ_0071542 could serve as a promising biomarker.

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Profiling and bioinformatics analysis of differentially expressed circular RNAs in human intervertebral disc degeneration

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmz036 ◽

2019 ◽

Vol 51 (6) ◽

pp. 571-579 ◽

Cited By ~ 7

Author(s):

Shunmin Wang ◽

Jingchuan Sun ◽

Haisong Yang ◽

Weiguo Zou ◽

Bing Zheng ◽

...

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Expression Profiles ◽

Differentially Expressed ◽

Circular Rnas ◽

Functional Changes ◽

Qrt Pcr ◽

Reverse Transcription Pcr ◽

Microarray Expression

AbstractThe functional changes of nucleus pulposus (NP) cells are considered to be the initiating factors of intervertebral disc degeneration (IDD), and the differentially expressed circRNAs in NP cells may play an important role in the process of IDD. To identify circular RNAs (circRNAs) associated with human IDD, we isolated the NP cells from human degenerated and non-degenerated intervertebral disc and identified NP cells by microscopy and cell proliferation. CircRNA microarray expression profiles were obtained from NP cells of degenerated and non-degenerated intervertebral disc and further validated by quantitative reverse transcription PCR (qRT-PCR). The expression data were analyzed by bioinformatics. Microarray analysis identified 7294 circRNAs differentially expressed in degenerated human IDD NP cells. Among them, 3724 circRNAs were up-regulated and 3570 circRNAs were down-regulated by more than 2 folds. After validating by qRT-PCR, we predicted the possible miRNAs of the top dysregulated circRNAs using TargetScan, and miRanda. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most modulated circRNAs regulate the viability, degradation, apoptosis and oxidative stress in NP cells, and the possible mechanism underlying IDD was discussed. These results revealed that circRNAs may play a role in IDD and might be a promising candidate molecular target for gene therapy.

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Microarray Expression Profile of Circular RNAs in Plasma from Primary Biliary Cholangitis Patients

Cellular Physiology and Biochemistry ◽

10.1159/000485487 ◽

2017 ◽

Vol 44 (4) ◽

pp. 1271-1281 ◽

Cited By ~ 8

Author(s):

Jiajia Zheng ◽

Zhenrong Li ◽

Tiancheng Wang ◽

Yang Zhao ◽

Yongfeng Wang

Keyword(s):

Expression Profile ◽

Expression Profiles ◽

Characteristic Curve ◽

Group Versus ◽

Target Prediction ◽

Differentially Expressed ◽

Circular Rnas ◽

Primary Biliary Cholangitis ◽

Healthy Controls ◽

Qrt Pcr

Background/Aims: Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases, including autoimmune diseases. However, their role in primary biliary cholangitis (PBC) remains unclear. Here, we aimed to determine the circRNA expression profile in plasma from PBC patients and further explore the value of circRNA in diagnosing PBC. Methods: CircRNA microarrays were used to determine circRNA expression profiles in plasma samples from 6 PBC patients and 6 healthy controls. Statistical analyses identified differentially expressed circRNAs, and these circRNAs were verified by qRT-PCR in 29 PBC patients and 30 healthy controls. MicroRNA (miRNA) target prediction software identified putative miRNA response elements (MREs), which were used to construct a map of circRNA-miRNA interactions for the differentially expressed circRNAs. Results: Our results indicated that there were 18 up-regulated and 4 down-regulated circular RNAs in the plasma from PBC patients compared with that from healthy individuals. Among the differentially expressed circRNAs, hsa_circ_402458 (P=0.0033), hsa_circ_087631 and hsa_circ_406329 (P=0.0185) were up-regulated, and hsa_circ_407176 (P=0.0066) and hsa_circ_082319 were down-regulated in the PBC group versus the healthy group as demonstrated by qRT-PCR. In particular, hsa_circ_402458 was significantly higher in PBC patients not receiving UDCA treatment than in PBC patients receiving UDCA treatment (P=0.0338). The area under the receiver operating characteristic curve for hsa_circ_402458 for diagnosing PBC was 0.710 (P=0.005). For hsa_circ_402458, two putative miRNA targets, hsa-miR-522-3p and hsa-miR-943, were predicted. Conclusions: circRNA dysregulation may play a role in PBC pathogenesis, and hsa_circ_402458 shows promise as a candidate biomarker for PBC.

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Identification of lncRNA–mRNA Regulatory Network Associated With Isolated Systolic Hypertension and Atherosclerotic Cerebral Infarction

10.21203/rs.3.rs-391143/v1 ◽

2021 ◽

Author(s):

jie Yang ◽

Yan-Nan Tao ◽

Fang-Xiao Hu ◽

Yong-Zhi Chen ◽

Xue-Song Yang ◽

...

Keyword(s):

Cerebral Infarction ◽

Regulatory Network ◽

Systolic Hypertension ◽

Expression Profiles ◽

Pearson Correlation ◽

Interaction Network ◽

Differentially Expressed ◽

Isolated Systolic Hypertension ◽

Hub Genes ◽

Qrt Pcr

Abstract Background: Increasing evidences uncover that lncRNAs play an important role in Isolated systolic hypertension (ISH). However, a systematic lncRNA-mRNA regulatory network is still absent in isolated systolic hypertension and atherosclerotic cerebral infarction patients (ISH & ACI).Aim:This research aims to establish a lncRNA-mRNA co-expression network in patients with ISH & ACI, to probe into the potential functions of lncRNA in those patients.Design and Setting:Expression profiles of lncRNA and mRNAs are collected and compared respectively from 8 patients with ISH and 8 patients with ISH & ACI by RNA-seq data.Methods: Differentially expressed lncRNAs and mRNAs were screened out via high-throughput sequencing in the plasma of ISH/ACI patients and control ISH patients. Then, a lncRNA-mRNA interaction network was built using the Pearson correlation coefficient by Cytoscape software. The expression levels of the hub genes and lncRNAs were verified by qRT-PCR in another 10 ISH/ACI patients and 10 control patients. Results: 2768 differentially expressed lncRNAs and 747 differentially expressed mRNAs were identified. 2 hub genes (CD226 and PARVB) and 11 lncRNAs were identified in the lncRNA-mRNA interaction network. qRT-PCR and cell assay results verified that lncRNAs ENST00000590604 and CD226 are highly expressed in patients of ISH & ACI. CD226 was associated with vascular endothelial cells growth and stability through platelet activation and focal adhesion pathway.Conclusion: We established a novel mRNA-lncRNA interaction network. lncRNAs ENST00000590604 and CD226 might be the potential biomarkers of ISH & ACI.

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Microarray based circRNA expression profiles in uremic plasma and PBMCs due to chronic glomerulonephritis

Archives of Biological Sciences ◽

10.2298/abs160520128w ◽

2017 ◽

Vol 69 (3) ◽

pp. 523-534 ◽

Cited By ~ 2

Author(s):

Xi Wang ◽

Yong Dai ◽

Wanfan Zhang ◽

S SunDonglin ◽

Xinzhou Zhang

Keyword(s):

Expression Profile ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Expression Profiles ◽

Expression Patterns ◽

Differentially Expressed ◽

Circular Rnas ◽

Chronic Glomerulonephritis ◽

Qrt Pcr ◽

Uremic Patients

Circular RNAs (circRNAs) have been identified in many diseases and shown to play important roles in pathological processes. The expression patterns of circRNA in uremia remains unknown. The aim of this study was to screen circRNA in plasma and peripheral blood mononuclear cells (PBMCs)in healthy controls and patients with uremia due to chronic glomerulonephritis, and to provide evidence for further exploration of the pathogenesis, diagnosis and treatment of uremic patients. Twenty individuals were included in this study, of which 10 were healthy and 10 were patients with uremia caused by chronic glomerulonephritis without systemic lupus erythematosus(SLE). Peripheral blood was collected from each individual in the two groups and the PBMCs were separated. The circRNAs expression profile was examined using a human circRNA microarray. The expression of differently expressed circRNAs was further validated by qRT-PCR. Seven hundred ten circRNAs were differentially expressed in the plasma in the two groups, accounting for 27.58% of the total circRNA(710/2578). Three hundred eighty-five up regulated circRNAs accounted for 14.93% and 325 down regulated circRNAs accounted for 12.60% of the total circRNAs. Additionally, 968 circRNAs were differentially expressed in PBMCs in the two groups, accounting for 29.24% of all circRNAs (968/3310).Six hundred seventy upregulated circRNAs accounted for 20.24% and 298 down regulated circRNAs accounted for 9.00% of the total circRNAs. The results of qRT-PCR validation were consistent with the microarray gene expression results. The expression profile of circRNAs was altered in the plasma and PBMCs of patients with uremia, which suggests that the changed circRNAs may be potential diagnostic biomarkers that play an important role in the pathogenesis of uremic patients. We speculate that hsa_circ_0053958, hsa_circ_0103281 may be associated with the pathogenesis of uremia and may be potential biological molecular markers for the diagnosis and prognosis of uremia.

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Circular Ribonucleic Acid Expression Profiles Differ Between the Plasma of Participants with Latent Autoimmune Diabetes in Adults and Healthy Individuals

10.21203/rs.3.rs-32901/v1 ◽

2020 ◽

Author(s):

Lili Ning ◽

Yan Yan ◽

Xiying Fu ◽

Yan Cheng ◽

Mo Li ◽

...

Keyword(s):

Diabetes Mellitus ◽

Metabolic Syndrome ◽

Autoimmune Diabetes ◽

Expression Profiles ◽

Differentially Expressed ◽

Circular Rnas ◽

Healthy Individuals ◽

Qrt Pcr ◽

Latent Autoimmune Diabetes ◽

New Biomarkers

Abstract Background: To investigate the characteristic expression of circular RNAs (circRNA) in the peripheral blood of individuals with latent autoimmune diabetes in adults (LADA) and healthy individuals(NG) to identify dysregulated circRNAs that could be used to differentiate between LADA and healthy individuals. Results: A total of 992 differentially expressed circRNAs were detected in the Group LA vs Group NG:209 circRNAs were significantly upregulated and 783 circRNAs downregulated.These circRNAs distributed on all chromosomes, including the sex chromosomes, and most of the differentially expressed circRNAs were derived from exons. Two circRNAs were identified as the most distinctive differentially expressed targets, hsa_circ_0097425 and newly-discovered circRNA-hsa_circ_62540520. We used qRT-PCR to verify the differentially expressed circRNAs, both circRNAs were statistically significant (p <0.05). Further studies have found that the two circRNAs may be associated with metabolic syndrome , inflammation and cell cycle.Conclusion: We determined that differentially expressed circRNAs could be used as new biomarkers for distinguishing LADA from healthy individuals. Further investigations may illustrate the partial pathogenesis of diabetes mellitus.Trial registration: ChiCTR, ChiCTR1900020644. Registered 11 January 2019, http://www.chictr.org.cn/showproj.aspx?proj=30591

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Identification of lncRNA–mRNA Regulatory Network Associated With Isolated Systolic Hypertension And Atherosclerotic Cerebral Infarction

10.21203/rs.3.rs-391143/v2 ◽

2021 ◽

Author(s):

Jie Yang ◽

Yan-Nan Tao ◽

Fang-Xiao Hu ◽

Yong-Zhi Chen ◽

Xue-Song Yang ◽

...

Keyword(s):

Cerebral Infarction ◽

Regulatory Network ◽

Systolic Hypertension ◽

Expression Profiles ◽

Pearson Correlation ◽

Interaction Network ◽

Differentially Expressed ◽

Isolated Systolic Hypertension ◽

Hub Genes ◽

Qrt Pcr

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Circular RNA Expression Profiles and Bioinformatic Analysis in Mouse Models of Obstructive Sleep Apnea-Induced Cardiac Injury: Novel Insights Into Pathogenesis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.767283 ◽

2021 ◽

Vol 9 ◽

Author(s):

Suxian Lai ◽

Lijun Chen ◽

Pingyun Zhan ◽

Guofu Lin ◽

Hai Lin ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Kegg Pathway ◽

Expression Profiles ◽

Cardiac Injury ◽

Differentially Expressed ◽

Circular Rnas ◽

Cardiac Tissues ◽

Qrt Pcr ◽

Obstructive Sleep

Circular RNAs (circRNAs) participate in the development of various kinds of diseases. However, the function and roles of circRNAs in obstructive sleep apnea (OSA)-induced cardiovascular disease remain poorly understood. Therefore, we sought to explore the circRNA expression profiles and predict their functions in OSA-induced cardiac injury with the use of bioinformatics analysis. The model of OSA was established in mouse treated by chronic intermittent hypoxia (CIH) exposure. Then, we screened the circRNA profile using circRNA microarray. By comparing circRNA expression in three matched pairs of CIH-treated cardiac tissues and controls, differentially expressed circRNAs were identified in the CIH groups. Comparison of the selected circRNAs expression levels was performed between qRT-PCR and microarray. Meanwhile, we employed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to predict the functions of these selected circRNAs. Finally, we constructed a circRNA-miRNA-mRNA network based on the target prediction. It was found that a total of 124 circRNAs were differentially expressed in CIH-treated cardiac tissues (p ≤ 0.05, fold-change ≥ 1.5). Among them, 23 circRNAs were significantly down-regulated, and the other 101 were up-regulated. Then, ten circRNAs were randomly selected to validate the reliability of the microarray results by using qRT-PCR. Next, we conducted the GO and KEGG pathway analysis to explore the parental genes functions of differentially expressed circRNA. Finally, two significantly differentially expressed circRNAs (mmu_circRNA_014309 and mmu_circRNA_21856) were further selected to create a circRNA-miRNA-mRNA regulation network. Our study did first reveal that the differentially expressed circRNAs played a vital role in the pathogenesis of OSA-induced cardiac damage. Thus, our findings bring us closer to unraveling the pathophysiologic mechanisms and eliciting novel therapeutic targets for the treatment of OSA-associated cardiovascular diseases.

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