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

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.

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.


2021 ◽  
Vol 21 (03) ◽  
Author(s):  
Jie Lu

ABSTRACT This study investigated expression profiles and mechanisms of circular RNAs on preeclampsia patients between 7-14 weeks. RNA sequencing demonstrated 12,579 circRNAs (7,684 upregulated and 4,895 downregulated) expressed differentially in 8 pairs of plasma samples from preeclampsia patients and healthy controls. Predicted 15 upregulated and 9 downregulated circRNAs then were assessed through qRT-PCR in 50 preeclampsia patients and 30 controls. Differentially expressed circRNAs in preeclampsia patients and controls were analyzed by RNA sequencing and gene ontology, Kyoto Encyclopedia of Genes and Genomes and circRNA-miRNA-mRNA network analyzed data. Hsa_circ_0046677 and hsa_circ_0029703 were markedly increased in preeclampsia patients. Receiver operator characteristic curve analysis indicated the area under the curve was 0.083 for hsa_circ_0046677 and 0.965 for hsa_circ_00429703 while the sensitivity and specificity of these two genes were 78 percent, 88 percent and 83 percent, 93 percent, respectively. Hsa_circ_0046677 and hsa_circ_00429703 had enormous potentials for diagnosing preeclampsia of pregnant women in the first trimester.


2021 ◽  
Author(s):  
Fei Yang ◽  
Feng Jing ◽  
Yang Li ◽  
Shanshan Kong ◽  
Shimin Zhang ◽  
...  

Abstract Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder associated with muscle weakness and small-cell lung cancer. Here, we used microarray analysis to identify long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) that might serve as biomarkers for LEMS.Methods: Plasma lncRNA and mRNA expression profiles of three patients with paraneoplastic LEMS and three healthy controls were analyzed using Arraystar Human lncRNA Microarray v4.0. Differentially expressed lncRNAs and adjacent mRNAs were analyzed jointly, and candidates were verified in individual samples by quantitative real-time polymerase chain reaction (qRT-PCR). The identified lncRNAs and mRNAs were evaluated in nine patients with paraneoplastic LEMS, eight patients with non-tumor LEMS, and four patients with small cell lung cancer (SCLC). Results: A total of 320 lncRNAs were differentially expressed in patients with paraneoplastic LEMS compared to healthy controls (fold change >1.5, P < 0.05), and nine were further evaluated. One of the identified lncRNAS, LOC338963 (NR_031439), is known to regulated the expression of the mRNA AP3B2, and both were upregulated more than 2-fold in patients with paraneoplastic LEMS compared to healthy controls. Furthermore, qRT-PCR analysis revealed significant upregulation of LOC338963 (NR_031439) and AP3B2 expression in patients with paraneoplastic LEMS compared to those with either non-tumor LEMS (2.37- and 5.06-fold, respectively) or SCLC (4.36- and 14.97-fold, respectively).Conclusions: Plasma LOC338963 (NR_031439) and AP3B2 were found to be upregulated in LEMS and might be used as diagnostic biomarkers for this disease.


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.


2018 ◽  
Author(s):  
Xingjie-Bao ◽  
Xin-He ◽  
Shuying-Zheng ◽  
Yizhe-Luo ◽  
Tianlun-Gu ◽  
...  

AbstractCircular RNAs (circRNAs), widely found in human cells, are involved in disease and play an important role in progression. To determine whether circRNAs are related in essential hypertension (EH), we analyzed the expression profile of circRNAs and miRNAs in 5 EH and 5 healthy controls cases which were screened by microarray. Through microarray data and public data analysis, differently expressed transcripts were divided into modules, and circRNAs were functionally annotated by miRNAs. The expression of two circRNAs, has_circ_0037909 and has_circ_0105015, were validated in EH by qRT-PCR, which may be associated with EH. Further analysis showed that two circRNAs might through immune system by up-regulation circRNAs and down-regulation expression. These circRNAs biological functions need to be further validated.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11420
Author(s):  
Haijin Zhang ◽  
Xue Song ◽  
Zongyan Teng ◽  
Sujun Cheng ◽  
Weigang Yu ◽  
...  

Background Osteoporosis (OP) is a systemic disease with bone loss and microstructural deterioration. Numerous noncoding RNAs (ncRNAs) have been proved to participate in various diseases, especially circular RNAs (circRNAs). However, the expression profile and mechanisms underlying circRNAs in male osteoporosis have not yet been explored. Methods The whole transcriptome expression profile and differences in mRNAs, circRNAs, and microRNAs (miRNAs) were investigated in peripheral blood samples of patients with osteoporosis and healthy controls consisting of males ≥ 60-years-old. Results A total of 398 circRNAs, 51 miRNAs, and 642 mRNAs were significantly and differentially expressed in osteoporosis compared to healthy controls. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the host genes of significantly differentially expressed circRNAs were mainly enriched in the regulation of cell cycle process: biological process (BP), organelle part cellular components (CC), protein binding molecular function (MF), Toll-like receptor signaling pathway, tumor necrosis factor (TNF) signaling pathway, and thyroid hormone signaling pathway. circRNA-miRNA-mRNA regulatory network was constructed using the differentially expressed RNAs. Moreover, key circRNAs (hsa_circ_0042409) in osteoporosis were discovered and validated by qPCR. Conclusions The key cicrRNAs plays a major role in the pathogenesis of osteoporosis and could be used as potential biomarkers or targets in the diagnosis and treatment of osteoporosis.


2020 ◽  
Author(s):  
Lili Ning ◽  
Yan Yan ◽  
Xiying Fu ◽  
Yan Cheng ◽  
Mo Li ◽  
...  

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


Author(s):  
Pan Ge ◽  
Jian Zhang ◽  
Liang Zhou ◽  
Mo-qi Lv ◽  
Yi-xin Li ◽  
...  

Abstract Background Non-obstructive azoospermia (NOA) is a multifactorial disorder whose molecular basis remains largely unknown. Circular RNAs (CircRNAs), a novel class of endogenous RNAs, have been recognized to play important roles in many biological processes. However, little is known about the expression patterns and functions of circRNAs in human testes involved in NOA. Methods In this study, the testicular circRNA expression profile were explored in NOA patients and the controls by high-throughput circRNA microarray. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm the microarray data. Bioinformatics analyses including the circRNA/miRNA/mRNA interaction network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to predict the functions of differentially expressed circRNAs. Results A total of 368 differentially down-regulated and 526 up-regulated circRNAs were detected in NOA patients. These findings have been verified by qRT-PCR on 6 selected circRNAs. Among these differentially expressed circRNAs, the hsa_circRNA_0023313 was obviously up-regulated in testicular tissue of NOA patients. The most likely potential target miRNA for hsa_circRNA_0023313 include hsa-miR-520d-3p, hsa-miR-373-3p, hsa-miR-372-3p, hsa-miR-302c-3p and hsa-miR-130b-5p. Function analysis indicated that hsa_circRNA_0023313 was ubiquitin-protein transferase activity and chromatin binding. KEGG analysis revealed that the top five pathways related to hsa_circRNA_0023313 were endocytosis, meiosis, FoxO signaling pathway, ubiquitin mediated proteolysis and AMPK signaling pathway. Conclusions This is the first report that the testicular circRNA expression profile is altered in NOA patients indicating circRNAs might play important roles in regulating spermatogenesis and be potential biomarkers for the diagnosis and treatment of NOA.


Author(s):  
Suxian Lai ◽  
Lijun Chen ◽  
Pingyun Zhan ◽  
Guofu Lin ◽  
Hai Lin ◽  
...  

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.


2021 ◽  
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.


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