Microarray Analysis Identifies Key Differentially Expressed Circular RNAs in Aged Mice With Postoperative Cognitive Dysfunction.
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ABSTRACT:
SUBMITTER: Wu YQ
PROVIDER: S-EPMC8415796 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Circulating RNA (circRNA) regulates various bioactivities in cells. A better understanding of the exosomal circRNA can provide novel insights into the pathogenesis and treatment of Graves' disease (GD). We aimed to profile the differentially expressed circRNAs (DEcRs) in plasma exosomes of patients with GD and speculate and probe the functions of the DEcR by comprehensive bioinformatics analyses. METHODS:Serum exosomes were isolated from five primary GD patients and five healthy controls via ultracentrifugation. After verification with transmission electron microscopy, exosome samples were subjected to microarray profiling using human circRNA microarrays. Two up-regulated and two down-regulated DEcRs were selected for validation in plasma exosomes from 20 GD and 20 healthy control participants using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). The circRNA/microRNA/mRNA interaction network was then assembled and the analysis of the Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was utilized to predict the potential functions of the DEcR associated genes. RESULTS:There were 15 DEcRs revealed in primary GD cases. The intronic circRNA hsa_circRNA_000102 was confirmed as an up-regulated component in plasma exosomes from patients with GD. The circRNA/microRNA/mRNA interaction network unveiled the most potential targeting microRNAs of hsa_circRNA_000102 and its associated genes. The functional analyses predicted involvement of hsa_circRNA_000102 associated genes in pathways of immune system activation, such as viral infection and interferon-beta signaling. CONCLUSIONS:hsa_circRNA_000102 is a differentially up-regulated plasma exosomal circRNA in patients with GD. Our study highlights multiple pathways, particularly virus infection and interferon-beta signaling, for mediating immune activation in Graves' disease.
| S-EPMC7388456 | biostudies-literature
Project description:BackgroundMiddle ear cholesteatoma is characterized by hyper-proliferation of keratinocytes. Circular RNA (circRNA) plays an essential role in the pathogenesis of many proliferative diseases. However, the role of circRNA in the etiopathogenesis of middle ear cholesteatoma is rarely investigated so far. We aimed to investigate the differential expression profiling of circRNAs between acquired middle ear cholesteatoma and normal skin, and to identify potential circRNAs contributing to the etiopathogenesis of middle ear cholesteatoma. Microarray analysis and functional prediction were performed to investigate the circRNA expression profiling between middle ear cholesteatoma and normal skin. Validation of differentially expressed circRNAs was conducted by qRT-PCR. Prediction of m6A modification was also carried out.ResultsMicroarray analysis displayed that totally 93 up-regulated and 85 down-regulated circRNAs were identified in middle ear cholesteatoma. Through validation, expressions of hsa_circRNA_104327 and hsa_circRNA_404655 were significantly higher, while hsa_circRNA_000319 was significantly down-regulated in cholesteatoma. GO classification, KEGG pathway, and ceRNA network analyses suggested that these differentially expressed circRNAs might play important roles in the etiopathogenesis of middle ear cholesteatoma. Prediction of m6A modification exhibited that hsa_circRNA_000319 possessed 4 m6A sites with very high confidence, and hsa_circRNA_404655 had 3 m6A sites with high confidence.ConclusionsOur study revealed that these differentially expressed circRNAs might contribute to the etiopathogenesis of middle ear cholesteatoma. Further researches should be conducted to investigate the exact mechanism of these differentially expressed circRNAs in the etiopathogenesis of middle ear cholesteatoma. Targeting on these circRNAs may provide a new strategy for middle ear cholesteatoma therapy in the future.
| S-EPMC8684697 | biostudies-literature
Project description:Background:Postoperative cognitive dysfunction (POCD) is one of the severe complications after surgery, inducing low life quality and high mortality, especially in elderly patients. However, the underlying molecular mechanism of POCD remains largely unknown, and the ideal biomarker for clinical diagnosis and prognosis is lacking. Circular RNAs (circRNAs), as a unique class of non-coding RNAs, were characterized by its stability and conservativeness, serving as novel biomarkers in various diseases. Nevertheless, the role of circRNAs in the occurrence of POCD remains elusive. Methods:To investigate the differentially expressed circRNAs in the serum of POCD patients and its potential role in the development of POCD, we performed a circRNA microarray to screen the differentially expressed circRNAs in the serum samples from three patients of the POCD group and three paired patients of the non-POCD group. Subsequently, quantitative real-time polymerase chain reaction analysis (qRT-PCR) was utilized to verify the microarray data with the serum samples from 10 paired patients. Cytoscape software was used to construct the circRNA-miRNA-mRNA network for circRNAs with different expression levels as well as the target genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed the biological functions of the differentially expressed circRNAs target genes. Results:In total, we have analyzed 10,198 circRNAs through the microarray. Compared with the non-POCD patient group, there were 210 differentially expressed circRNAs with 133 upregulated and 77 downregulated in the POCD group (?2-fold differential expression, P ? 0.05). The qRT-PCR confirmed 10 circRNAs with different expressed levels, and the results were consistent with the microarray findings. Among them, hsa_circRNA_001145, hsa_circRNA_101138, and hsa_circRNA_061570 had the highest magnitude of change. The GO analysis showed that the differentially expressed circRNAs were associated with the regulation of the developmental process, cell-to-cell adhesion, and nervous system development. The KEGG analysis showed that the target genes of circRNAs were enriched in the MAPK signaling pathway and RAS signaling pathway. According to the targetscan7.1 and mirdbV5 databases, the circRNA-miRNA-mRNA network was constructed, and these results provided a vital landscape of circRNA expression profile in POCD. Conclusions:Our study provides an essential perspective for the differential expression of circRNAs in POCD patients. Further studies need to be performed to explore their potential therapeutic roles in the development of POCD.
| S-EPMC7324535 | biostudies-literature
Project description: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.
| S-EPMC8424120 | biostudies-literature
Project description:Allergic asthma is one of the most common allergic diseases; however, the mechanisms underlying its development have yet to be fully elucidated. Although allergic diseases are inheritable, genetic variance alone cannot explain the notable increase in the prevalence of allergic diseases over a short period of time in recent decades. Recently, research focus has been shifting to epigenetic factors, such as non‑coding RNAs. Circular RNAs (circRNAs) are involved in the pathogenesis of various diseases. The aim of the present study was to further elucidate the etiology of allergic asthma by analyzing aberrantly expressed circRNAs in a murine asthma model. A mouse model of house dust mite allergen‑induced asthma was established, and the qualified libraries were sequenced using next‑generation sequencing. The expression levels of circRNAs were validated by reverse transcription‑quantitative PCR (RT‑qPCR) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for biological pathway classification and enrichment analysis of the aberrantly expressed circRNAs. In addition, the interaction network of the differentially expressed circRNAs and microRNAs (miRNAs) was constructed using Cytoscape. By next‑generation sequencing, a total of 150 circRNAs were revealed to be upregulated and 130 were downregulated in the murine asthma model group compared with in the control group. GO and KEGG analyses demonstrated that the differentially expressed circRNAs were mainly involved in processes such as 'autoimmune disease', 'cell adhesion molecules (CAMs)' and 'endocytosis', among others. The expression levels of six circRNAs, namely three upregulated (circ_0000909, circ_0000629 and circ_0000455) and three downregulated (circ_0001454, circ_0000723 and circ_0001389) circRNAs, were validated by RT‑qPCR. In conclusion, the analyses suggested that circRNAs performed critical functions via endocytosis (such as macrophage endocytosis), cell adhesion molecules and lipid metabolism in allergic asthma. The interaction network revealed that certain miRNAs that may serve a role in asthma could be regulated by the differentially expressed circRNAs.
| S-EPMC7647044 | biostudies-literature
Project description:Postoperative cognitive dysfunction (POCD) is a common postoperative complication observed in elderly patients. However, the underlying mechanisms of POCD remain unclear. MicroRNAs (miRNAs) which are involved in the pathogenesis of neurodegenerative diseases, may also affect POCD. To identify the relevant potential mechanisms, in this study, we comprehensively compared the expression profiles of miRNAs in 5 hippocampal tissues from POCD mice and 5 hippocampal tissues from control mice by microarray. A total of 128 miRNAs, whose expression changed significantly, were identified. Four miRNAs were confirmed by quantitative real-time polymerase chain reaction (PCR) in 10 paired samples. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed to explore the principal functions of the deregulated genes. We predicted the potential targets of miRNAs by using bioinformatics methods. In summary, novel miRNAs were identified as potential biomarkers and therapeutic targets for POCD treatment.
2017-02-20 | GSE95070 | GEO
Project description:Postoperative cognitive dysfunction (POCD) is a significant complication of surgery, particularly in elderly patients. Emerging researches showed that long non-coding RNA (lncRNA) may play a vital role in the pathogenesis of POCD. Here we aimed to identify potential key lncRNAs involved in the development of POCD. LncRNA and mRNA expression profiles in hippocampal tissues from POCD and control mice were analyzed by microarray assay. Gene ontology (GO) and KEGG pathway enrichment analyses were conducted to probe the functions of dysregulated genes. Then, important factors of the mainly affected biological processes were measured in the hippocampus. Correlated coding-non-coding co-expression (CNC) networks were constructed. Finally, the potential key pairs of lncRNA and target mRNA implicated in POCD were probed. Our data showed that 868 differentially expressed lncRNAs and 690 differentially expressed mRNAs were identified in total. GO and KEGG analyses indicated that the differentially expressed genes were mainly associated with inflammatory and apoptotic signaling pathways. Surgery-induced inflammatory cytokines and apoptosis were significantly increased in hippocampal tissues of aged mice. In CNC network analysis, we found that LncRNA uc009qbj.1 was positively correlated with apoptosis-associated gene Vrk2 level. LncRNA ENSMUST00000174338 correlated positively with expression of the inflammation and apoptosis-associated gene Smad7. LncRNA NONMMUT00000123687 mediated gene expression by binding the inflammation-regulated transcription factor Meis2. Our results suggested that these potential key lncRNAs and mRNAs may play a crucial role in the development of POCD through mediating neuronal inflammation or apoptosis.
| S-EPMC6650538 | biostudies-literature
Project description:Apoptosis is a form of regulated cell death that plays a critical role in survival and developmental homeostasis. There are numerous reports on regulation of apoptosis by protein-coding genes as well as small non-coding RNAs, such as microRNAs. However, there is no comprehensive investigation of circular RNAs (circRNA) that are differentially expressed under apoptotic conditions. We have performed a transcriptomics study in which we first triggered apoptosis in HeLa cells through treatment with four different agents, namely cisplatin, doxorubicin, TNF-α and anti-Fas mAb. Total RNAs isolated from control as well as treated cells were treated with RNAse R to eliminate the linear RNAs. The remaining RNAs were then subjected to deep-sequencing to identify differentially expressed circRNAs. Interestingly, some of the dys-regulated circRNAs were found to originate from protein-coding genes well-documented to regulate apoptosis. A number of candidate circRNAs were validated with qPCR with or without RNAse R treatment as well. We then took advantage of bioinformatics tools to investigate the coding potential of differentially expressed RNAs. Additionally, we examined the candidate circRNAs for the putative miRNA-binding sites and their putative target mRNAs. Our analyses point to a potential for circRNA-mediated sponging of miRNAs known to regulate apoptosis. In conclusion, this is the first transcriptomics study that provides a complete circRNA profile of apoptotic cells that might shed light onto the potential role of circRNAs in apoptosis.
| S-EPMC6424894 | biostudies-literature
Project description:Postoperative cognitive dysfunction (POCD) is one of the severe complications inducing low life quality and high mortality after surgery, especially in elderly patients.Here we probed differentially expressed circRNAs using microarray assay in POCD patients, aiming to find potential key circRNAs related to the occurrence of POCD. Subsequently, ten dysregulated circRNAs were confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) in 10 paired samples. Then, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to probe the vital functions of dysregulated genes.
2020-07-14 | GSE147277 | GEO
Project description:Circular RNA (circRNA) has been well studied in many diseases, whereas their role in patients with postoperative cognitive dysfunction (POCD) remains largely unclear. Here, we investigated the therapeutic effects of dexmedetomidine (Dex) on POCD and analyzed the role of circRNA as well as the pathways that may be involved. The Morris water maze test demonstrated that POCD rats have a longer incubation period than the normal group, but the latency of POCD rats was significantly lower after Dex treatment. Moreover, HE staining showed that Dex improved hippocampal pathological changes. RNA sequencing showed 164 differentially expressed circRNAs between POCD and Dex groups; 74 were upregulated and 90 were downregulated in the Dex group. A total of 20,790 target genes for differentially expressed circRNAs were observed in RNAhybrid and Miranda databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the target genes of differentially expressed circRNAs are mainly focused on positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage, negative regulation of cell adhesion mediated by integrin, and response to cytokines and other function of life activities and involved in the P53 signaling pathway and nuclear factor kappa B (NF-κB) signaling pathway. Furthermore, the expression of five candidate circRNAs (circ-Shank3, circ-Cdc42bpa, circ-chrx-24658, cir-chr17-3642 and circ-Sgsm1) and target genes were consistent with the RNA sequencing results, which was verified by quantitative real-time polymerase chain reaction (qRT-PCR). These results indicate that circ-Shank3 participate in the process of Dex improved POCD through regulating the P53 and NF-κB signaling pathways and may potentially facilitate POCD treatment through the development of clinical drugs.
| S-EPMC7093639 | biostudies-literature