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

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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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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CircRNA expression profile and functional analysis in testicular tissue of patients with non-obstructive azoospermia

Reproductive Biology and Endocrinology ◽

10.1186/s12958-019-0541-4 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 3

Author(s):

Pan Ge ◽

Jian Zhang ◽

Liang Zhou ◽

Mo-qi Lv ◽

Yi-xin Li ◽

...

Keyword(s):

Signaling Pathway ◽

Expression Profile ◽

Function Analysis ◽

Expression Patterns ◽

Testicular Tissue ◽

Differentially Expressed ◽

Circular Rnas ◽

Transferase Activity ◽

Obstructive Azoospermia ◽

Qrt Pcr

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.

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Regional variations in ABC transporter expression along the mouse intestinal tract

Physiological Genomics ◽

10.1152/physiolgenomics.00150.2003 ◽

2004 ◽

Vol 17 (1) ◽

pp. 11-20 ◽

Cited By ~ 40

Author(s):

David M. Mutch ◽

Pascale Anderle ◽

Muriel Fiaux ◽

Robert Mansourian ◽

Karine Vidal ◽

...

Keyword(s):

Gene Expression ◽

Abc Transporter ◽

Expression Profile ◽

Abc Transporters ◽

Intestinal Tract ◽

Expression Profiles ◽

Expression Patterns ◽

Assessment Model ◽

Differentially Expressed ◽

Distal Intestine

The ATP-binding cassette (ABC) family of proteins comprise a group of membrane transporters involved in the transport of a wide variety of compounds, such as xenobiotics, vitamins, lipids, amino acids, and carbohydrates. Determining their regional expression patterns along the intestinal tract will further characterize their transport functions in the gut. The mRNA expression levels of murine ABC transporters in the duodenum, jejunum, ileum, and colon were examined using the Affymetrix MuU74v2 GeneChip set. Eight ABC transporters (Abcb2, Abcb3, Abcb9, Abcc3, Abcc6, Abcd1, Abcg5, and Abcg8) displayed significant differential gene expression along the intestinal tract, as determined by two statistical models (a global error assessment model and a classic ANOVA, both with a P < 0.01). Concordance with semiquantitative real-time PCR was high. Analyzing the promoters of the differentially expressed ABC transporters did not identify common transcriptional motifs between family members or with other genes; however, the expression profile for Abcb9 was highly correlated with fibulin-1, and both genes share a common complex promoter model involving the NFκB, zinc binding protein factor (ZBPF), GC-box factors SP1/GC (SP1F), and early growth response factor (EGRF) transcription binding motifs. The cellular location of another of the differentially expressed ABC transporters, Abcc3, was examined by immunohistochemistry. Staining revealed that the protein is consistently expressed in the basolateral compartment of enterocytes along the anterior-posterior axis of the intestine. Furthermore, the intensity of the staining pattern is concordant with the expression profile. This agrees with previous findings in which the mRNA, protein, and transport function of Abcc3 were increased in the rat distal intestine. These data reveal regional differences in gene expression profiles along the intestinal tract and demonstrate that a complete understanding of intestinal ABC transporter function can only be achieved by examining the physiologically distinct regions of the gut.

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Circular RNA expression profiles and bioinformatic analysis in coronary heart disease

Epigenomics ◽

10.2217/epi-2019-0369 ◽

2020 ◽

Vol 12 (5) ◽

pp. 439-454 ◽

Cited By ~ 2

Author(s):

Fangpu Yu ◽

Yuanyuan Tie ◽

Ya Zhang ◽

Zunzhe Wang ◽

Liwen Yu ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Coronary Arteries ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Expression Profiles ◽

Peripheral Blood Mononuclear ◽

Qrt Pcr ◽

Blood Mononuclear Cells

Aim: We aimed to identify the expression profile and role of circular RNAs (circRNAs) in coronary heart disease (CHD). Materials & methods: We performed sequence analysis of circRNAs in peripheral blood mononuclear cells of 70 CHD patients and 30 controls. Eight selected circRNAs were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in human atherosclerotic coronary arteries. Results: In total, 2283 downregulated and 85 upregulated circRNAs were identified in CHD. Parental genes of top 100 dysregulated-circRNAs are related to metabolism and protein modification, and 12 circRNAs might upregulate their CHD-related parental genes through miRNA sponges. Of the eight circRNAs validated in atherosclerotic coronary arteries by qRT-PCR, six were consistent with sequencing results of peripheral blood mononuclear cells. Conclusion: As potential ceRNAs, dysregulated circRNAs may be involved in CHD pathophysiology.

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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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Expression Profile of Circular RNAs in Epicardial Adipose Tissue in Heart Failure

10.1101/764266 ◽

2019 ◽

Author(s):

Meili Zheng ◽

Lei Zhao ◽

Xinchun Yang

Keyword(s):

Heart Failure ◽

Adipose Tissue ◽

Expression Profile ◽

Epicardial Adipose Tissue ◽

Expression Profiles ◽

Expression Patterns ◽

Circular Rna ◽

Circular Rnas ◽

Artery Disease ◽

Pathway Analyses

AbstractRecent studies have reported circular RNA (circRNA) expression profiles in various tissue types; specifically, a recent work showed a detailed circRNA expression landscape in the heart. However, circRNA expression profile in human epicardial adipose tissue (EAT) remains undefined. RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease (CAD) cases between the heart failure (HF) and non-HF groups. The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response, including KIAA0182, RHOBTB3, HIPK3, UBXN7, PCMTD1, N4BP2L2, CFLAR, EPB41L2, FCHO2, FNDC3B and SPECC1. Among the 141 circRNAs substantially different between the HF and non-HF groups (P<0.05;fold change>2), hsa_circ_0005565 stood out, and was mostly associated with positive regulation of metabolic processes and insulin resistancein GO and KEGG pathway analyses, respectively. These data indicate EAT circRNAs contribute to the pathogenesis of metabolic disorders causing HF.

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Characteristics of circular RNAs expression of peripheral blood mononuclear cells in humans with Coronary Artery Disease

Physiological Genomics ◽

10.1152/physiolgenomics.00020.2021 ◽

2021 ◽

Author(s):

Wen-Feng Ji ◽

Jia-Xin Chen ◽

Shu He ◽

Ya-Qing Zhou ◽

Lei Hua ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Differentially Expressed ◽

Circular Rnas ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Artery Disease

Objective: Circular RNAs (circRNAs) function as promising biomarkers and therapeutic targets for coronary artery disease due to their high stability, covalently closed structure and potential gene regulation. We aimed to identify the expression profile and role of circular RNAs (circRNAs) in coronary artery disease (CAD). Methods: We performed RNA sequence analysis of circRNAs in peripheral blood mononuclear cells of 5 CAD patients and 5 controls. Bioinformatics analyses was adopted to explore biological functions of differentially expressed circRNAs. The miRanda and TargetScan tools were used to predict the miRNA targeting interactions and to construct a triple network of differentially expressed gene-circRNA-miRNA-mRNA. Results: In total, 13160 downregulated and 12905 upregulated circRNAs were identified in CAD. A gene ontology annotation analysis showed that genes in the network were involved in organelle organization, cell cycle, mitotic cycle and cellular metabolic process. Parental genes of the 10 dysregulated-circRNAs were involved in metabolism and protein modification, and these circRNAs might regulate gene expression associated with CAD via miRNA sponges. Conclusion: As potential ceRNAs, dysregulated circRNAs may be involved in the pathogenesis of CAD, which provides new insights into diagnosis and prognosis of coronary artery disease.

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Transcriptomic Analysis of circRNAs in the Peripheral Blood of Nonarteritic Anterior Ischemic Optic Neuropathy

BioMed Research International ◽

10.1155/2020/5732124 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Jinshan Suo ◽

Xinling Xu ◽

Haoyan Xu ◽

Naifang Hou ◽

Jiaming Zhang ◽

...

Keyword(s):

Expression Profile ◽

Optic Neuropathy ◽

Peripheral Blood ◽

High Throughput Sequencing ◽

Expression Profiles ◽

Interaction Network ◽

Original Data ◽

Anterior Ischemic Optic Neuropathy ◽

Circular Rnas ◽

Ischemic Optic Neuropathy

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.

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Expression Profile and Potential Function of Circular RNAs in Peripheral Blood Mononuclear Cells in Male Patients With Primary Gout

Frontiers in Genetics ◽

10.3389/fgene.2021.728091 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fei Dai ◽

Quan-Bo Zhang ◽

Yi-Ping Tang ◽

Yi-Xi He ◽

Ting Yi ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Fold Change ◽

Differentially Expressed ◽

Circular Rnas ◽

Peripheral Blood Mononuclear ◽

Expression Levels ◽

Primary Gout ◽

Blood Mononuclear Cells

Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) with a single-stranded covalently closed-loop structure, and their abnormal expression may participate in the pathogenesis of various human diseases. Currently, knowledge of circRNAs in gout is limited. In this case-control study, human circRNA microarrays were used to identify differentially expressed circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with primary gout (n = 5) and healthy controls (HC; n = 3). Bioinformatics methods were used to analyze significantly different circRNAs (fold change >1.5, p < 0.05). In addition, four significantly differentially expressed circRNAs were selected for quantitative real-time polymerase chain reaction to detect expression levels in 90 gout patients and 60 HC. Subsequently, circRNA-miRNA-mRNA network was established to predict the function of circRNAs of interest. Microarray analysis indicated that 238 circRNAs were upregulated and 41 circRNAs were down-regulated in the gout group (fold change >1.5, p < 0.05). Bioinformatics analysis showed that differentially expressed circRNAs were involved in the pathogenesis of gout via various pathways. Moreover, the expression levels of hsa_circRNA_103657 and hsa_circRNA_000241 were significantly higher in the gout group than those in the HC group, and both correlated significantly with lipid metabolism parameters. Furthermore, the area under the curve of hsa_circRNA_103657 was 0.801 (95% confidence interval (CI): 0.730–0.871; p < 0.001). Our results provide novel insights into the pathogenesis of primary gout. Differentially expressed circRNAs were identified in the PBMCs of gout patients, and these differential circRNAs may play important roles in the development and progression of gout.

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Data Mining Identifies Differentially Expressed Circular RNAs in Skeletal Muscle of Thermally Challenged Turkey Poults

Frontiers in Physiology ◽

10.3389/fphys.2021.732208 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kent M. Reed ◽

Kristelle M. Mendoza ◽

Juan E. Abrahante ◽

Sandra G. Velleman ◽

Gale M. Strasburg

Keyword(s):

Gene Expression ◽

Data Mining ◽

Growth And Development ◽

Expression Profiles ◽

Expression Patterns ◽

Regulation Of Gene Expression ◽

Muscle Growth ◽

Differentially Expressed ◽

Circular Rnas ◽

Turkey Poults

Precise regulation of gene expression is critical for normal muscle growth and development. Changes in gene expression patterns caused by external stressors such as temperature can have dramatic effects including altered cellular structure and function. Understanding the cellular mechanisms that underlie muscle growth and development and how these are altered by external stressors are crucial in maintaining and improving meat quality. This study investigated circular RNAs (circRNAs) as an emerging aspect of gene regulation. We used data mining to identify circRNAs and characterize their expression profiles within RNAseq data collected from thermally challenged turkey poults of the RBC2 and F-lines. From sequences of 28 paired-end libraries, 8924 unique circRNAs were predicted of which 1629 were common to all treatment groups. Expression analysis identified significant differentially expressed circRNAs (DECs) in comparisons between thermal treatments (41 DECs) and between genetic lines (117 DECs). No intersection was observed between the DECs and differentially expressed gene transcripts indicating that the DECs are not simply the result of expression changes in the parental genes. Comparative analyses based on the chicken microRNA (miRNA) database suggest potential interactions between turkey circRNAs and miRNAs. Additional studies are needed to reveal the functional significance of the predicted circRNAs and their role in muscle development in response to thermal challenge. The DECs identified in this study provide an important framework for future investigation.

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