Bioinformatics Analysis of circRNA Expression and Construction of “circRNA-miRNA-mRNA” Competing Endogenous RNAs Networks in Bipolar Disorder Patients

Bipolar disorder (BD) is a severe mood disorder disease in China, and its underlying pathogenesis remains unknown. Circular RNAs (circRNAs) have been reported to play a key role in mental disorders and can be used as competitive endogenous RNAs (ceRNAs). However, little is known about the correlation of circRNAs with BD. In this study, Deep RNA sequencing was used to identify differentially expressed circRNAs (DE-circRNAs) and differentially expressed mRNAs (DE-mRNAs) between BD patients and a control group. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to validate the differentially expressed RNAs (DE-RNAs). In all 9,593 circRNAs and 20,030 mRNAs were found in the two groups of specimens, among which 50 DE-circRNAs and 244 DE-mRNAs were significantly upregulated, and 44 DE-circRNAs and 294 DE-mRNAs were significantly downregulated. Based on the regulatory mechanism of ceRNAs, circRNAs can directly bind microRNAs (miRNAs) to affect mRNA expression, and the expression trends of circRNAs and mRNAs are consistent. According to this mechanism, we constructed two ceRNA networks by using the RNA sequencing data. The function of these DE-circRNAs was further elucidated by enrichment analysis. In summary, the present study showed that the circRNA expression profile of BD patients is altered, and a ceRNA regulatory network was constructed, which provided a hypothesis about the pathogenesis of BD.

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Integrated Analysis of a circRNA-miRNA-mRNA Axis in Intervertebral Disc Degeneration

10.21203/rs.3.rs-129853/v1 ◽

2020 ◽

Author(s):

Laifu Wei ◽

Bizhi Tu ◽

Fei Gao ◽

Jun Qian

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Underlying Mechanism ◽

Differentially Expressed ◽

Circular Rnas ◽

Integrated Analysis ◽

Control Group ◽

Common Symptom ◽

Sequencing Data

Abstract Background: Low back pain (LBP) is a common symptom in daily life and one of the primary causes is intervertebral disc degeneration (IDD). Growing studies have indicated that circular RNAs (circRNAs) are intimately associated with IDD; however, the underlying mechanism has not yet been elucidated. We aimed to explore how circRNAs regulate IDD in an effort to provide novel insight for clinical diagnosis and treatment. Methods: The sequencing data of circRNAs, microRNAs (miRNAs), and mRNA were acquired from Gene Expression Omnibus (GEO) datasets. By analyzing the dataset consisting of a control group and degenerated group, differentially expressed circRNAs, miRNAs, and mRNAs were collected, and then the intersection of circRNAs, miRNAs, and mRNAs was screened. According to these intersectional RNAs, we constructed an integrally circRNA-miRNA-mRNA network. Finally, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we further clarified functions of the intersectional mRNA in IDD. Results: we obtained 620 differentially expressed circRNAs(DEcircRNAs), 13 miRNA (DEmiRNA), 273 mRNAs(DEmRNAs), 12 intersectional miRNAs, and 47 intersectional mRNAs. Finally, based on interactional 8 circRNA, 5 miRNAs and 15 mRNAs, an integrally circRNA-miRNA-mRNA network was constructed. Eight circRNAs, contained hsa_circ_0032254, hsa_circ_0003183, hsa_circ_0032253, hsa_circ_0001293, hsa_circ_0004565, hsa_circ_0091570, hsa_circ_0077526, and hsa_circ_0057552, may regulate IDD onset and progression by acting as competing endogenous RNAs. The results of GO and KEGG analyses implied that the targeted genes might significantly correlate to IDD.Conclusion: our findings improved a better understanding of the circRNA-related ceRNA regulatory mechanism in IDD and offered possible targets for IDD treatment.

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Identification and comparison of circular RNAs in preeclampsia

PeerJ ◽

10.7717/peerj.11299 ◽

2021 ◽

Vol 9 ◽

pp. e11299

Author(s):

Zepeng Ping ◽

Ling Ai ◽

Huaxiang Shen ◽

Xing Zhang ◽

Huling Jiang ◽

...

Keyword(s):

Rna Sequencing ◽

Gestational Hypertension ◽

Interaction Analysis ◽

Expression Patterns ◽

Enrichment Analysis ◽

Circular Rnas ◽

Pathway Enrichment Analysis ◽

Sequencing Data ◽

Mortality And Morbidity ◽

Specific Syndrome

Background Preeclampsia (PE) is a pregnancy-specific syndrome, belongs to the gestational hypertension diseases category and is considered among the causes of maternal and perinatal mortality and morbidity. However, the pathogenesis of PE is still vague. Methods In the present study, the circular RNA (circRNA) expression patterns of normal pregnant women and PE patients were investigated using whole RNA sequencing. Results A total of 151 differential expressed circRNAs were identified including 121 upregulated and 30 downregulated ones. Functional and pathway enrichment analysis was conducted on the differentially expressed circRNAs using Gene Ontology and KEGG databases. The results of this analysis indicated that several crucial biological processes and pathways were enriched in PE patients. circRNA–microRNA (miRNA) interaction analysis indicated that the reported differentially expresse circRNAs may be associated with some regulatory functions through miRNAs in PE patients. Two ceRNAs networks were constructed according to the targeting relationship between circRNAs/miRNAs and miRNAs/mRNAs. One sub-network contained one upregulated circRNA, four downregulated miRNAs and five upregulated mRNAs, and another sub-network contained 10 downregulated circRNAs, 21 upregulated miRNAs and 15 downregulated mRNAs. Conclusion CircRNA expression patterns have been investigated and this analysis revealed their potential regulatory mechanisms in PE patients. We constructed the ceRNAs (competing endogenous RNA) to reveal the potential molecular roles of dysregulated circRNAs in the PE patients using RNA sequencing data. circRNA_13301 was the only one upregulated circRNA in ceRNA being targeted by four miRNAs.

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Identification and Characterization of Serum microRNAs as Biomarkers for Human Disc Degeneration: An RNA Sequencing Analysis

Diagnostics ◽

10.3390/diagnostics10121063 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1063

Author(s):

Shangbin Cui ◽

Zhiyu Zhou ◽

Xizhe Liu ◽

Robert Geoff Richards ◽

Mauro Alini ◽

...

Keyword(s):

Rna Sequencing ◽

Disc Degeneration ◽

Lumbar Disc ◽

Young Patients ◽

Differentially Expressed ◽

Control Group ◽

Sequencing Analysis ◽

Circulating Mirnas ◽

Sequencing Data ◽

Ivd Degeneration

Circulating microRNAs (miRNAs) have been associated with various degenerative diseases, including intervertebral disc (IVD) degeneration. Lumbar disc herniation (LDH) often occurs in young patients, although the underlying mechanisms are poorly understood. The aim of this work was to generate RNA deep sequencing data of peripheral blood samples from patients suffering from LDH, identify circulating miRNAs, and analyze them using bioinformatics applications. Serum was collected from 10 patients with LDH (Disc Degeneration Group); 10 patients without LDH served as the Control Group. RNA sequencing analysis identified 73 differential circulating miRNAs (p < 0.05) between the Disc Degeneration Group and Control Group. Gene ontology enrichment analysis (p < 0.05) showed that these differentially expressed miRNAs were associated with extracellular matrix, damage reactions, inflammatory reactions, and regulation of apoptosis. Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed genes were involved in diverse signaling pathways. The profile of miR-766-3p, miR-6749-3p, and miR-4632-5p serum miRNAs was significantly enriched (p < 0.05) in multiple pathways associated with IVD degeneration. miR-766-3p, miR-6749-3p, and miR-4632-5p signature from serum may serve as a noninvasive diagnostic biomarker for LHD manifestation of IVD degeneration. Furthermore, several dysregulated miRNAs may be involved in the pathogenesis of IVD degeneration. Further study is needed to confirm the functional role of the identified miRNAs.

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Analysis of the Molecular Mechanism of Acute Coronary Syndrome Based on circRNA-miRNA Network Regulation

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/1584052 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17 ◽

Cited By ~ 1

Author(s):

Fei Lin ◽

YaMing Yang ◽

Quan Guo ◽

Mingzhang Xie ◽

Siyu Sun ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Interaction Network ◽

Enrichment Analysis ◽

Pathological Process ◽

Differentially Expressed ◽

Circular Rnas ◽

Control Group ◽

Coronary Syndrome ◽

Biological Technology ◽

Group A

Background. With the development of biological technology, biomarkers for the prevention and diagnosis of acute coronary syndrome (ACS) have become increasingly evident. However, the study of novel circular RNAs (circRNAs) in ACS is still in progress. This study aimed to investigate whether the regulation of circRNA-miRNA networks is involved in ACS pathogenesis. Methods. We used microarray analysis to detect significantly expressed circRNAs and miRNAs in the peripheral blood of patients in the control group (CG) and ACS groups, including an unstable angina pectoris (UAP) group and an acute myocardial infarction (AMI) group. A circRNA-miRNA interaction network analysis was carried out with open-source bioinformatics. The gene ontology (GO), pathway, and disease enrichment analyses for differentially expressed circRNAs were further analysed with hierarchical clustering. Results. A total of 266 circRNAs (121 upregulated and 145 downregulated, P<0.05, fold change FC ≥2) and 3 miRNAs (1 upregulated and 2 downregulated, P<0.05, FC ≥ 1.2) were differentially expressed in the ACS groups compared with those in the CG. In addition, among these expressed circRNAs and miRNAs, a single circRNA could bind to more than 1–100 miRNAs, and vice versa. Next, an AMI-UAP network, an AMI-CG network, a UAP-CG network, and an AMI-CG-UAP network were constructed. The top 30 enriched GO terms among the three groups were emphasized as differentially expressed. Disease enrichment analysis showed that these differentially expressed circRNAs are involved in the pathogenesis of cardiovascular diseases. KEGG pathway analysis was performed to identify pathways associated with circRNAs targeting mRNAs. Conclusion. CircRNAs are closely related to the pathological process of ACS via a mechanism that may be related to the up- or down-regulation of circRNAs and miRNAs and circRNA-miRNA coexpression. The metabolic pathways, signalling pathways, and diseases affected by these circRNAs can be predicted by enrichment analysis.

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Differentially Expressed Circular RNA Profile in an Intracranial Aneurysm Group Compared with a Healthy Control Group

Disease Markers ◽

10.1155/2021/8889569 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Yonggang Ma ◽

Baoqing Zhang ◽

Dong Zhang ◽

Shuo Wang ◽

Maogui Li ◽

...

Keyword(s):

Intracranial Aneurysm ◽

Profile Analysis ◽

Circular Rna ◽

Differentially Expressed ◽

Circular Rnas ◽

Control Group ◽

Expression Profile Analysis ◽

Healthy Control ◽

Polymerase Chain

Objective. Intracranial aneurysm (IA) is a fatal disease owing to vascular rupture and subarachnoid hemorrhage. Much attention has been given to circular RNAs (circRNAs) because they may be potential biomarkers for many diseases, but their mechanism in the formation of IA remains unknown. Methods. circRNA expression profile analysis of blood samples was conducted between patients with IA and controls. Overall, 235 differentially expressed circRNAs were confirmed between IA patients and the control group. The reliability of the microarray results was demonstrated by quantitative real-time polymerase chain reaction (qRT-PCR). Results. Of 235 differentially expressed genes, 150 were upregulated, while the other 85 were downregulated. Five miRNAs matched to every differential expression of circRNAs, and related MREs were predicted. We performed gene ontology (GO) analysis to identify the functions of their targeted genes, with the terms “Homophilic cell adhesion via plasma membrane adhesion molecules” and “Positive regulation of cellular process” showing the highest fold enrichment. Conclusions. This study demonstrated the role of circRNA expression profiling in the formation of IA and revealed that the mTOR pathway can be a latent therapeutic strategy for IA.

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Target identification of hepatic fibrosis using Pien Tze Huang based on mRNA and lncRNA

Scientific Reports ◽

10.1038/s41598-021-96459-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jinhang Zhu ◽

Di Zhang ◽

Ting Wang ◽

Zhiliang Chen ◽

Luan Chen ◽

...

Keyword(s):

Liver Injury ◽

Hepatic Fibrosis ◽

Drug Targets ◽

Enrichment Analysis ◽

Inflammatory Cells ◽

Differentially Expressed ◽

Control Group ◽

Traditional Chinese Herbal Medicine ◽

Hepatic Diseases ◽

Pien Tze Huang

AbstractHepatic fibrosis is a spontaneous wound-healing response triggered by chronic liver injury. Pien Tze Huang (PZH), a traditional Chinese herbal medicine, has been widely used to treat various hepatic diseases in Asia. We used a CCl4-induced mouse model to establish a PZH group of hepatic fibrosis mice treated with PZH and a control group of hepatic fibrosis mice without any treatment. We performed RNA-seq and mass spectrometry sequencing to investigate the mechanism of the PZH response in hepatic fibrosis and identified multiple differentially expressed transcripts (DETs) and proteins (DEPs) that may be drug targets of PZH. Liver functional indices, including serum albumin (ALB), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly decreased in the PZH treatment group (P < 0.05) in the eighth week. Hematoxylin–eosin (HE), Masson and Sirius red staining demonstrated that PZH significantly inhibited infiltration of inflammatory cells and collagen deposition. A total of 928 transcripts and 138 proteins were differentially expressed in PZH-treated mice compared to the control group. Gene Ontology (GO) enrichment analysis suggested that PZH may alleviate liver injury and fibrosis by enhancing the immune process. Taken together, our results revealed that multiple DETs and DEPs may serve as drug targets of PZH in hepatic fibrosis patient in future clinical practice.

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MicroRNA expression profiling involved in Borax-induced anti-tumor effect using gene-chip analysis

10.21203/rs.2.20621/v1 ◽

2020 ◽

Author(s):

Lun Wu ◽

Ying Wei ◽

Wen-Bo Zhou ◽

Jiao Zhou ◽

Li-Hua Yang ◽

...

Keyword(s):

Signaling Pathway ◽

Hepg2 Cells ◽

Enrichment Analysis ◽

Gene Chip ◽

Differentially Expressed ◽

Control Group ◽

Pathway Enrichment Analysis ◽

Ras Signaling ◽

Therapeutic Benefits ◽

Differentially Expressed Mirnas

Abstract Background Borax, a boron compound, which is becoming widely recognized for its biological effects, including antioxidant activity, cytotoxicity, and potential therapeutic benefits. However, the specific molecular mechanisms underlying borax-induced anti-tumor effect still remain to be to further elucidated. MicroRNAs (miRNAs) may play key roles in cellular processes including tumor progression, cell apoptosis and cytotoxicity. Thus, this study aimed to investigate, whether miRNAs were involved in the borax-mediated anti-tumor effect using miRNA profiling of a human liver cancer cell line (HepG2) using gene-chip analysis.Methods Total RNA was extracted and purified from HepG2 cells that were treated with 4 mM borax for either 2 or 24 h. The samples underwent microarray analysis using an Agilent Human miRNA Array. Differentially expressed miRNAs were analysed by volcano plot and heatmap, and were validated using real-time fluorescent quantitative PCR (qPCR).ResultsAmong this, 2- or 24-h exposure to borax significantly altered the expression level of miRNAs in HepG2 cells, 4 or 14 were upregulated and 3 were downregulated compared with the control group, respectively (≥2-fold; P<0.05). GO enrichment analysis and KEGG pathway enrichment analysis revealed that target genes of differentially expressed miRNAs in HepG2 cells predominantly participated in MAPK signaling pathway, TGF-beta signaling pathway, NF-kappa B signaling pathway, etc; in 2-h borax treatment group, while Ras signaling pathway, FoxO signaling pathway, Cellular senescence, etc; involved in 24-h treatment group.Conclusions Result indicates that borax-induced anti-tumor effect may be associated with alterations in miRNAs.

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Expression Profiling of Circular RNAs and Micrornas in Heart Tissue of Mice with Alcoholic Cardiomyopathy

Cellular Physiology and Biochemistry ◽

10.1159/000489596 ◽

2018 ◽

Vol 46 (6) ◽

pp. 2284-2296 ◽

Cited By ~ 5

Author(s):

Yuqiao Yang ◽

Hongmei Chen ◽

Nina Ding ◽

Shuo Wang ◽

Zhantao Duan ◽

...

Keyword(s):

Alcohol Consumption ◽

Signaling Pathways ◽

Treated Group ◽

Heart Tissue ◽

Differentially Expressed ◽

Circular Rnas ◽

Control Group ◽

Alcoholic Cardiomyopathy ◽

Bioinformatics Software ◽

Heavy Alcohol Consumption

Background/Aims: Chronic heavy alcohol consumption may result in alcoholic cardiomyopathy. This study was designed to screen differentially expressed microRNAs and circular RNAs in heart tissue of mice with alcoholic cardiomyopathy to reveal the underlying molecular mechanism. Methods: Having established a murine alcoholic cardiomyopathy model, we screened differentially expressed microRNAs and circular RNAs in three heart samples from the alcohol-treated and control groups by high-throughput microarray analysis. We analyzed the function and biological signaling pathways of differentially expressed non-coding RNAs closely related to alcoholic cardiomyopathy using bioinformatics software to identify some mRNAs and their biological signaling pathways closely related to alcoholic cardiomyopathy. Results: Nineteen microRNAs and 265 circular RNAs were differentially expressed in the alcohol-treated group compared with the control group. After analyzing gene function and signaling pathways by bioinformatics software, we found that the differentially expressed mRNAs were associated with carbohydrate metabolism. Conclusions: Chronic alcohol consumption can change the non-coding RNA profile of heart tissue, which is closely related to the pathological mechanisms of alcoholic cardiomyopathy.

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Proteomic analysis of tears and serum for dry eye disease using ovariectomized cynomolgus monkey

10.21203/rs.2.21889/v1 ◽

2020 ◽

Author(s):

xiaolong yang ◽

Yue Xu ◽

Yun Wang ◽

Chang Li ◽

Xiaofeng Zhang

Keyword(s):

Gene Ontology ◽

Growth Factor ◽

Dry Eye ◽

Cynomolgus Monkey ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Control Group ◽

Differentially Expressed Proteins ◽

Dry Eyes ◽

Experimental Group

Abstract Background Ovariectomized cynomolgus monkey 30 months after surgery was selected as the research object to identify protein changes in tears and serum to provide a reference for the diagnosis and pathogenesis of dry eye in menopausal women. Methods Six cynomolgus monkey were randomly divided into an experimental group and a control group (3 in each group). The experimental group underwent bilateral ovariectomy, while the control group underwent sham surgery with their ovaries reserved. Proteomic analysis was performed by LC-MS/MS on tears and serum collected from two groups. Differentially expressed proteins were identified and were performed cluster analysis, which included gene ontology, the Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction. Results 33 differentially expressed proteins have been identified in tears and17 differentially expressed proteins have been identified in serum. Kyoto Encyclopedia of Genes and Genomes enrichment analysis in tears has discovered Glucagon signaling pathway and neurotrophin signaling pathway may play an important role in the pathogenesis of dry eye. Gene ontology enrichment analysis in serum has discovered insulin-like growth factor binding and growth factor binding in molecular function probably make effort in pathogenesis of dry eye. KEGG analysis in serum has discovered salivary secretion may be the key pathway in pathogenesis of dry eye. Conclusions Protein G7PCH4, Q2PG17 and G7PT55 in tears may be the key protein in pathogenesis of dry eyes. Protein G7P1T1, G7PUN9 and G8F302 in serum may play an important role in pathogenesis of dry eyes.

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