scholarly journals Circular Ribonucleic Acid Expression Profiles Differ Between the Plasma of Participants with Latent Autoimmune Diabetes in Adults and Healthy Individuals

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

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 ◽  
Vol 25 (2(98)) ◽  
pp. 125-129
Author(s):  
I. Tsaryk ◽  
N. Pashkovska ◽  
O. Ilashchuk

The aim of the study. To determine the prevalence of risk factors for cardiometabolic complications in latent autoimmune diabetes in adults compared to other types of diabetes depending on the phenotype of the disease.Materials and methods. A comprehensive examination of 106 patients with diabetes mellitus: 45 (main group) with latent autoimmune diabetes in adults (LADA), 26 - with type 1 diabetes mellitus (T1DM), 35 - with type 2 diabetes mellitus (T2DM). Complaints, anamnesis data, objective examination, results of general clinical, laboratory researches, indicators of carbohydrate metabolism, titers of antibodies to glutamic acid decarboxylase were evaluated.Results. The prevalence of metabolic syndrome (MS) in LADA was 51% and was significantly higher than in T1DM (19%), but was lower compared with T2DM (94%). The highest incidence of MS was found in patients with the LADA2 phenotype (87%). Of particular note is the fact that this figure was close to that in T2DM. At the same time in LADA1 the incidence of MS was lower (36%), but twice as high as in T1DM. In addition to hyperglycemia, abdominal obesity (62% of patients), hypertension (78%) and dyslipidemia (56%) were commonly reported in LADA.Conclusions. The prevalence of metabolic syndrome as a complex of cardiometabolic risk factors in LADA differs from that in classical types of diabetes, which requires a differential approach to their management.


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.


2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Zhang Pengyu ◽  
Yan Yan ◽  
Fu Xiying ◽  
Yang Maoguang ◽  
Li Mo ◽  
...  

Background. Long noncoding RNAs (lncRNAs) were previously found to be closely related to the pathogenesis of diabetes. Objectives. To reveal the differentially expressed lncRNAs and messenger RNAs (mRNAs) involved in type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults (LADA) and predict the lncRNA target genes to derive their expression profiles for the diagnosis of T2DM and LADA and their differential diagnosis. Methods. Twelve venous blood samples were collected from T2DM patients, LADA patients, and nondiseased subjects to obtain total RNAs. After removing rRNA from total RNAs to establish the desired library for sequencing, quality control and quantification analyses were carried out. The fragments per kilobase of exon model per million reads mapped (FPKM) of lncRNAs were calculated to construct the gene expression profiles of lncRNAs and mRNAs. Fold changes (fold change: 2.0) and p values (p value: 0.05, FPKM ≥ 0.1) were calculated, and then differentially expressed lncRNAs and mRNAs were screened. To obtain the significantly coexpressed lncRNA-mRNA pairs, the lncRNA target genes were deduced according to the association between adjacent sites. Results. Compared to nondiseased controls, 68,763 versus 28,523 lncRNAs and 133 versus 1035 mRNAs were significantly upregulated and significantly downregulated, respectively, in T2DM patients. For LADA patients, 68,748 versus 28,538 lncRNAs and 219 versus 805 mRNAs were significantly upregulated and significantly downregulated, respectively, relative to nondiseased controls. Compared to T2DM patients, 74,207 versus 23,079 lncRNAs and 349 versus 137 mRNAs were significantly upregulated and significantly downregulated, respectively, in LADA patients. Based on the correlation analysis, seven lncRNA-mRNA pairs (BTG2, A2M, HECTD4, MBTPS1, DBH, FLVCR1, and NCBP2) were significantly coexpressed, and two lncRNAs (ENST00000608916 and ENST00000436373) were newly discovered. Conclusion. Significant differences in lncRNA expression were discovered among the three groups. Furthermore, after predicting lncRNA expression profiles, GO/KEGG pathway analysis could deduce the target gene function.


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.


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 &lt; 0.05) and 899 down-regulated (fold change ≥2, P &lt; 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 &lt; 0.001), has_circ_0070186 up-regulation (2.82-fold, P &lt; 0.001), and has_circ_0069972 down-regulation (0.50-fold, P &lt; 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.


Author(s):  
Han-Wen Chen ◽  
Xiao-Xia Zhang ◽  
Zhu-Ding Peng ◽  
Zu-Min Xing ◽  
Yi-Wen Zhang ◽  
...  

AbstractTreatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.


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