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

Author(s):  
Lili Lan ◽  
Yu Liu ◽  
Menglin Zou ◽  
Yihang Xie ◽  
Yiye Zhang ◽  
...  

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.

2020 ◽  
Vol 7 ◽  
Author(s):  
Wei Sun ◽  
Bo Han ◽  
Dongxiao Cai ◽  
Jing Wang ◽  
Diandong Jiang ◽  
...  

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.


2018 ◽  
Vol 50 (3) ◽  
pp. 936-951 ◽  
Author(s):  
Jun-Hui Yang ◽  
Run-Jiao Zhang ◽  
Jia-Jie Lin ◽  
Ming-Chao Cao ◽  
Qie Wang ◽  
...  

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.


2019 ◽  
Vol 51 (6) ◽  
pp. 571-579 ◽  
Author(s):  
Shunmin Wang ◽  
Jingchuan Sun ◽  
Haisong Yang ◽  
Weiguo Zou ◽  
Bing Zheng ◽  
...  

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.


2017 ◽  
Vol 44 (4) ◽  
pp. 1271-1281 ◽  
Author(s):  
Jiajia Zheng ◽  
Zhenrong Li ◽  
Tiancheng Wang ◽  
Yang Zhao ◽  
Yongfeng Wang

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.


2021 ◽  
Author(s):  
jie Yang ◽  
Yan-Nan Tao ◽  
Fang-Xiao Hu ◽  
Yong-Zhi Chen ◽  
Xue-Song Yang ◽  
...  

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.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Jinshan Suo ◽  
Xinling Xu ◽  
Haoyan Xu ◽  
Naifang Hou ◽  
Jiaming Zhang ◽  
...  

The aim of the study is to explore the expression profile variation of circular RNAs (circRNAs) in the peripheral blood of subjects with nonarteritic anterior ischemic optic neuropathy (NAION) and without NAION, to analyze the differential expression results, and to predict the role of circRNAs in disease development, providing novel ideas and methods for treatment and diagnosis. High-throughput sequencing to explore the expression profiles of RNAs in the peripheral blood of 6 NAION patients and 5 healthy controls was applied. Quality control obtained the advanced data from the original data by ticking out the unqualified data. Then, cluster analysis, volcano plot, coexpression network, and protein-protein interaction network (PPI) were performed. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to analyze the whole expressed genes. Lastly, the quantitative real-time Polymerase Chain Reaction (qRT-PCR) was used to verify those significantly differentially expressed circRNAs and do some bioinformatics analysis and prediction in 12 NAION patients and 12 controls. There were significant differences in the expression of 49 circRNAs in the peripheral blood of NAION patients, in which there were 24 upregulations and 25 downregulations (variation folds > 2 and P < 0.05 ), and it was confirmed that hsa_circ_0005583, hsa_circ_0003922, hsa_circ_0002021, and hsa_circ_0000462 were significantly downregulated (variation folds > 2 and P < 0.05 ), especially hsa_circ_0005583 which was the most significantly changed one ( P < 0.001 ), and are related to processes such as neurodegeneration, oxidative stress, immunity, and metabolism. The expression profile of circRNAs in the peripheral blood of NAION patients is significantly changed, enriching our understanding of the disease.


2021 ◽  
Vol 49 (2) ◽  
pp. 94-103
Author(s):  
Jie Chen ◽  
Xiyan Xiao ◽  
Shan He ◽  
Yi Qiao ◽  
Shuwei Ma

Background: Emerging evidence shows that circular RNAs (circRNAs) participate in the pathogenesis of multiple immune diseases. However, few studies have focused on the mechanisms of circRNAs involved in allergic rhinitis (AR). Methods: This study performed an RNA sequence (RNA-seq) profiling to identify the expression of circRNAs in nasal mucosa from ovalbumin-induced AR murine models and normal controls. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) was then conducted to validate the differential expression of circRNAs. Bioinformatics analysis was applied to demonstrate the biological functions of the dysregulated circRNAs. Results: A total of 86 distinct circRNA candidates were sequenced, of which 51 were upregulated and 35 were downregulated. The T cell receptor, B cell receptor, and calcium signaling pathways may be involved in the pathology of AR. Furthermore, a circRNA-miRNA interaction network was constructed via miRNA response elements analysis. Some circRNAs were cor-related with miRNAs that are involved in T cell polarization and activation, thereby highlighting their potential role in the pathogenesis of AR. Conclusions: This study demonstrates a number of aberrantly expressed circRNAs related to AR, and offers a novel perspective into AR pathogenesis and future therapeutic strategies.


Author(s):  
Hailiang Yu ◽  
Changhao Mi ◽  
Qi Wang ◽  
Wenbin Zou ◽  
Guojun Dai ◽  
...  

Coccidiosis is an important intestinal parasitic disease that causes great economic losses to the global poultry production industry. Circular RNAs (circRNAs) are long non-coding RNAs that play important roles in various infectious diseases and inflammatory responses. However, the expression profiles and functions of circRNAs during Eimeria tenella (E. tenella) infection remain unclear. In this study, high-throughput sequencing was carried out to detect circRNAs in chicken cecal tissues from the control (JC), resistant (JR), and susceptible (JS) groups on day 4.5 postinfection (pi), respectively. A total of 104 circRNAs were differentially expressed, including 47 circRNAs between the JS and JC groups, 38 between the JR and JS groups, and 19 between the JR and JC groups. Functional analyses indicated that these differentially expressed circRNAs were involved in pathways related to E. tenella infection; the adaptive immune response was enriched in the JS vs JC group, the NF-kappa B signaling and natural killer cell-mediated cytotoxicity pathways were enriched in the JS vs JC and JR vs JC groups, while the B cell receptor signaling pathway was enriched in only the JR vs JC group. Moreover, the coexpression network of differentially expressed circRNAs and mRNAs suggested that circRNA2202 and circRNA0759 associated with DTX1 in the JS vs JC group, circRNA4338 associated with VPREB3 and CXCL13L3 in the JR vs JC group, and circRNA2612 associated with IL8L1 and F2RL2 in the JR vs JS group were involved in the immune response upon E. tenella infection. In conclusion, our results provide valuable information on the circRNAs involved in the progression of chicken E. tenella infection and advance our understanding of the circRNA regulatory mechanisms of host resistance and susceptibility to E. tenella infection in chickens.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Junfu Guo ◽  
Xiangnan Li ◽  
Lanying Miao ◽  
Hongwei Sun ◽  
Xia Gao ◽  
...  

Objective. The present study aimed to investigate the potential mechanism underlying the antitumor effect of Si Jun Zi Tang (SJZT) decoction on gastric cancer. Methods. Twelve human gastric cancer SGC7901 cell xenograft nude mouse models were established. The mice were randomly divided into the Model group and SJZT group. SJZT exerted significant antitumor effects after 21 days of decoction administration. High-throughput sequencing was used to analyze the microRNA (miRNA) expression profiles of tumor tissues. Bioinformatics analysis was performed to provide further information regarding the differentially expressed miRNAs. Five representative differentially expressed miRNAs and four predicted target genes were further validated using quantitative real-time reverse transcription PCR (qRT-PCR). Results. We identified 33 miRNAs that were differentially expressed in the SJZT group compared with the Model group. Among them, 32 miRNAs were upregulated and 1 miRNA was downregulated. Bioinformatic analysis showed that most of miRNAs acted as tumor suppressors and their target genes participated in multiple signaling pathways, including the PI3K/Akt signaling pathway, microRNAs in cancer, and Wnt signaling pathway. The qRT-PCR result confirmed that miR-223-3p, miR-205-5p, miR-147b-3p, and miR-223-5p were overexpressed and their respective paired target genes FUT9, POU2F1, MUC4, and RAB14 mRNA were obviously downregulated in the SJZT group compared with those in the Model group. Network analysis revealed that miR-223-3p and miR-205-5p shared two targets POU2F1 (encoding POU class 2 homeobox 1) and FUT9 (encoding fucosyltransferase 9), suggesting they have a common role in certain pathways. Conclusion. This study provided novel insights into the anticancer mechanism of SJZT against gastric cancer, which might be partly related to the modulation of miRNA expression and their target pathways in tumors.


2017 ◽  
Vol 69 (3) ◽  
pp. 523-534 ◽  
Author(s):  
Xi Wang ◽  
Yong Dai ◽  
Wanfan Zhang ◽  
S SunDonglin ◽  
Xinzhou Zhang

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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