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

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.

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

2019 ◽  
Vol 51 (6) ◽  
pp. 571-579 ◽  
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.

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
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.

Gene Expression Profiles of Tumor Necrosis Factor-α and Endothelin-1 in Obstructive Sleep Apnea

ORL ◽  
2018 ◽  
Vol 81 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Kadriye Serife Ugur ◽  
Muradiye Acar ◽  
Duygu Ozol ◽  
Elif Dagli ◽  
Murat Oznur ◽  
...  
Keyword(s):  
Gene Expression ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Obstructive Sleep ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Circulating microRNA profile as a potential biomarker for obstructive sleep apnea diagnosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Fernando Santamaria-Martos ◽  
Iván Benítez ◽  
Francisco Ortega ◽  
Andrea Zapater ◽  
Cristina Giron ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Differentially Expressed ◽  
Mirna Profile ◽  
Circulating Microrna ◽  
Circulating Mirna ◽  
Cpap Treatment ◽  
Potential Biomarker ◽  
Obstructive Sleep ◽  
Differentially Expressed Mirnas

Abstract Evaluation of microRNAs (miRNAs) could allow characterization of the obstructive sleep apnea (OSA) and help diagnose it more accurately. We aimed to examine circulating miRNA profiles to establish the differences between non-OSA and OSA patients. Additionally, we aimed to analyse the effect of continuous positive airway pressure (CPAP) treatment on the miRNA profile. This observational, longitudinal study included 230 subjects referred to the Sleep Unit due to suspected OSA. Expression profiling of 188 miRNAs in plasma was performed in 27 subjects by TaqMan-Low-Density-Array. OSA-related miRNAs were selected for validation by RT-qPCR in 203 patients. Prediction models were built to discriminate between non-OSA and OSA: 1) NoSAS-score, 2) differentially expressed miRNAs, and 3) combination of NoSAS-score plus miRNAs. The differentially expressed miRNAs were measured after 6 months of follow-up. From the 14 miRNAs selected for validation, 6 were confirmed to be differentially expressed. The areas under the curve were 0.73 for the NoSAS-score, 0.81 for the miRNAs and 0.86 for the combination. After 6 months of CPAP treatment, miRNA levels in the OSA group seem to approximate to non-OSA levels. A cluster of miRNAs was identified to differentiate between non-OSA and OSA patients. CPAP treatment was associated with changes in the circulating miRNA profile.

scholarly journals MicroRNA expression profile is altered in the upper airway skeletal muscle tissue of patients with obstructive sleep apnea-hypopnea syndrome

2019 ◽  
Vol 47 (9) ◽  
pp. 4163-4182
Author(s):  
Jin Hou ◽  
Lei Zhao ◽  
Jing Yan ◽  
Xiaoyong Ren ◽  
Kang Zhu ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Expression Profiles ◽  
Upper Airway ◽  
Target Prediction ◽  
Mirna Array ◽  
Real Time Quantitative Pcr ◽  
Reverse Transcription Pcr ◽  
Obstructive Sleep ◽  
Hypopnea Syndrome

Objective To investigate the involvement of microRNAs (miRNAs) in the pathogenesis of obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods In this study, we investigated miRNA profiles in the upper airway (UA) skeletal muscles of four patients with OSAHS and four matched controls using the miRCURY miRNA array. In another cohort of 12 OSAHS cases and 7 controls, the mRNA expression levels of interleukin (IL)-6 and Lin-28 homolog A (Lin28A), targets of the downregulated let-7 family members, were measured by real-time quantitative-PCR. The potential targets of the miRNAs were predicted by miRNA target prediction databases miRanda, Microcosm, and Targetscan. Results The array identified 370 differentially expressed miRNAs, of which 181 were upregulated and 189 were downregulated in OSAHS patients (based on a fold-change >2.0 and p < 0.05). Upregulation of IL-6 and Lin28A was validated by quantitative reverse transcription PCR. The 612 targets predicted by all three algorithms were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The results revealed perturbations in signaling pathways and cellular functions. Conclusion This study demonstrated profoundly altered miRNA expression profiles in upper airway muscular tissues of patients with OSAHS, which might contribute to the formation and development of OSAHS.

scholarly journals Construction of a circRNA - Mediated ceRNA Network Reveals Novel Biomarkers for Aortic Dissection

2021 ◽  
Author(s):  
De-Bin Liu ◽  
You-Fu He ◽  
Gui-Jian Chen ◽  
Hua Huang ◽  
Xu-Ling Xie ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Kegg Pathway ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Qrt Pcr ◽  
Cerna Network ◽  
Arterial Blood

Abstract Background Aortic dissection (AD) is a rare and lethal disorder with its genetic basis remains largely unknown. Many studies have confirmed that circular RNAs (circRNAs) play important roles in various physiological and pathological processes. However, the roles of circRNAs in AD are still unclear and need further investigation. The present study aimed to elucidate the underlying molecular mechanisms of circRNAs regulation in aortic dissection based on the circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network. Methods Expression profiles of circRNAs (GSE97745), miRNAs (GSE92427), and mRNAs (GSE52093) were downloaded from Gene Expression Omnibus (GEO) databases, and the differentially expressed RNAs (DERNAs) were subsequently identified in AD by bioinformatics analysis. Further bioinformatics analyses, including circRNA-miRNA-mRNA ceRNA network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, were used to predict the potential functions of circRNA-associated ceRNA regulatory network. RNA was isolated from human arterial blood samples after which quantitative real-time PCR (qRT-PCR) was performed to confirm the DERNAs. Results We identified 14 (5 up-regulated and 9 down-regulated) differentially expressed circRNAs (DEcircRNAs), 17 (8 up-regulated and 9 down-regulated) differentially expressed miRNAs (DEmiRNAs) and 527 (297 up-regulated and 230 down-regulated) differentially expressed mRNAs (DEmRNAs) when AD samples were compared with normal ascending aorta samples (adjusted P-value < 0.05 and | log2FC |> 1.0). KEGG pathway analysis indicated that DEmRNAs were related to focal adhesion and extracellular matrix (ECM) receptor interaction signaling pathways. Simultaneously, the present study successfully constructed a ceRNA regulatory network based on 1 circRNAs (hsa_circRNA_082317), 1 miRNAs (hsa-miR-149-3p) and 10 mRNAs (MLEC, ENTPD7, SLC16A3, SLC7A8, TBC1D16, PAQR4, MAPK13, PIK3R2, ITGA5, SERPINA1) in AD. Furthermore, qRT-PCR demonstrated that hsa_circRNA_082317 andα5 integrin (ITGA5) were significantly up-regulated in AD (n = 3), and hsa-miR-149-3p was dramatically down-regulated in AD (n = 3). The expression of hsa-miR-149-3p target mRNA, ITGA5, was positively modulated by hsa_circRNA_082317. Conclusion This is the first study to demonstrate the circRNA-associated ceRNA regulatory network is altered in AD, implying that circRNAs may play important roles in regulating the onset and progression of AD and thus may serve as potential biomarkers for the diagnosis and treatment of AD.

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

2017 ◽  
Vol 69 (3) ◽  
pp. 523-534 ◽  
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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