Dataset Information

Microarray and bioinformatics analysis of circular RNAs expression profile in traumatic lung injury.

ABSTRACT: Acute lung injury (ALI) and respiratory distress syndrome are common, potentially lethal injuries that predominantly occur following chest trauma. Circular RNAs (circRNAs) are stable conserved non-coding RNAs that are widely expressed in different organs. To the best of our knowledge, no previous studies have shown whether circRNAs are involved in traumatic lung injury (TLI). The aim of the present study was to identify highly expressed circRNAs in plasma samples from patients with TLI and explore their potential functions in the pathogenesis of TLI. A high-throughput circRNA microarray was used to investigate the expression profile of circRNAs in plasma samples from five patients with TLI and paired control samples. Subsequently, a total of five abnormally expressed circRNAs were investigated using reverse transcription-quantitative PCR (RT-qPCR). A bioinformatics analysis was performed to predict a competitive endogenous RNA (ceRNA) network. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify the main biological processes and pathways. Finally, additional samples were tested to identify the expression profiles of the selected circRNAs. Among the 310 circRNAs that were highly expressed in the microarray analysis, 60 were upregulated and 250 were downregulated in patients with TLI. RT-qPCR results indicated that two downregulated circRNAs (circ_102927 and circ_100562) and one upregulated circRNA (circ_101523) matched the microarray results. The bioinformatics analysis constructed a targeting network based on the three validated circRNAs. GO and KEGG analyses identified the top ten enriched annotations. The expression of homo sapiens circular RNA 102927 (hsa_circRNA_102927) in the plasma of patients with TLI was 0.34-fold compared with the control group in expanded size validation. The results of the present study identified the differentially expressed circRNAs in the plasma of patients with TLI and provided evidence that highly expressed circRNAs involved in the ceRNA network may serve a role in the pathophysiology of TLI.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC7271735 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Microarray and bioinformatics analysis of circular RNAs expression profile in traumatic lung injury.

Jiang Yong Y Zhu Feng F Wu Guo-Sheng GS Wang Kang-An KA Wang Chen C Yu Qing Q Zhu Bang-Hui BH Sun Yu Y Xia Zhao-Fan ZF

Experimental and therapeutic medicine 20200423 1

Acute lung injury (ALI) and respiratory distress syndrome are common, potentially lethal injuries that predominantly occur following chest trauma. Circular RNAs (circRNAs) are stable conserved non-coding RNAs that are widely expressed in different organs. To the best of our knowledge, no previous studies have shown whether circRNAs are involved in traumatic lung injury (TLI). The aim of the present study was to identify highly expressed circRNAs in plasma samples from patients with TLI and explo ...[more]

PMID: 32509009

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Project description:BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is a rare but debilitating and life-threatening complication of acute pulmonary embolism. Circular RNAs (circRNAs), presenting as covalently closed continuous loops, are RNA molecules with covalently joined 3'- and 5'-ends formed by back-splicing events. circRNAs may be significant biological molecules to understand disease mechanisms and to identify biomarkers for disease diagnosis and therapy. The aim of this study was to investigate the potential roles of circRNAs in CTEPH.MethodsTen human blood samples (5 each from CTEPH and control groups) were included in the Agilent circRNA chip. The differentially expressed circRNAs were evaluated using t test, with significance set at a P value of < .05. A functional enrichment analysis for differentially expressed circRNAs was performed using DAVID online tools, and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for target genes of miRNAs was performed using the R package clusterProfiler. Furthermore, miRNAs that interacted with differentially expressed circRNAs were predicted using the miRanda package. mRNAs that had clear biological functions and were regulated by miRNAs were predicted using miRWalk2.0 and then combined into a circRNA-miRNA-mRNA network.ResultsIn total, 351 differentially expressed circRNAs (122 upregulated and 229 downregulated) between CTEPH and control groups were obtained; among these circRNAs, hsa_circ_0002062 and hsa_circ_0022342 might be important because they can regulate 761 (e.g., hsa-miR-942-5p) and 453 (e.g., hsa-miR-940) miRNAs, respectively. Target genes (e.g., cyclin-dependent kinase 6) of hsa-miR-942-5p were mainly enriched in cancer-related pathways, whereas target genes (e.g., CRK-Like Proto-Oncogene, Adaptor Protein) of hsa-miR-940 were enriched in the ErbB signaling pathway. Therefore, these pathways are potentially important in CTEPH.ConclusionsOur findings suggested that hsa_circ_0002062 and hsa_circ_0022342 may be key circRNAs for CTEPH development and that their targeted regulation may be an effective approach for treating CTEPH.

Project description:Spinal cord injury (SCI) is mostly caused by trauma. As primary mechanical injury is unavoidable in SCI, a focus on the pathophysiology and underlying molecular mechanisms of SCI-induced secondary injury is necessary to develop promising treatments for SCI patients. Circular RNAs (circRNAs) are associated with various diseases. Nevertheless, studies to date have not yet determined the functional roles of circRNAs in traumatic SCI. We examined circRNA expression profiles in the contused spinal cords of rats using microarray and quantitative reverse transcription-PCR (qRT-PCR) then predict their potential roles in post-SCI pathophysiology with bioinformatics. We found a total of 1676 differentially expressed circRNAs (fold change ? 2.0; P < 0.05) in spinal cord 3 days after contusion using circRNA microarray; 1261 circRNAs were significantly downregulated, whereas the remaining 415 were significantly upregulated. Then, five selected circRNAs, namely, rno_circRNA_005342, rno_circRNA_015513, rno_circRNA_002948, rno_circRNA_006096, and rno_circRNA_013017 were all significantly downregulated in the SCI group after verification by qRT-PCR, demonstrating a similar expression pattern in both microarray and PCR data. The next section of the study was concerned with the prediction of circRNA/miRNA/mRNA interactions using bioinformatics analysis. In the final part of the study, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses indicated carbohydrate metabolic process was one of the most significant enrichments and meaningful terms after GO analysis, and the top two signaling pathways affected by the circRNAs-miRNAs axes were the AMP-activated protein kinase signaling pathway and the peroxisome related pathway. In summary, this study showed an altered circRNA expression pattern that may be involved in physiological and pathological processes in rats after traumatic SCI, providing deep insights into numerous possibilities for SCI treatment targets by regulating circRNAs.

Project description:Recent studies have found that circular RNAs (circRNAs) play crucial roles not only in the normal growth and the development of different tissues and organs but also in the pathogenesis and progression of various disorders. However, the expression patterns and the function of circRNAs in acute ischemic stroke (AIS) in the South Chinese Han population are unclear. In the present study, RNA sequencing (RNA-seq) data was generated from 3 AIS patients and 3 healthy controls. The circRNAs were detected and identified by CIRI2 and Find_circ software. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses were used to detect the expression of circRNAs. Meanwhile, the potential diagnostic value of the selected circRNAs for AIS was assessed by generating receiver operating characteristic (ROC) curve with area under curve (AUC). The bioinformatic analysis of the host genes of differentially expressed (DE) circRNAs was performed by gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, KOBAS for pathway analysis and regulatory network analysis. miRNA-circRNA and miRNA-mRNA interactions were predicted by using TargetScan, miRanda and starBase. CircRNA-miRNA-mRNA interaction networks were created with Cytoscape. Our result showed that there were 2270 DE circRNAs between AIS patients and healthy controls. Among them, 659 were found upregulated and 1611 were downregulated. Bioinformatic analysis showed that the DE circRNAs were related to the following biological processes: endocytosis, energy metabolism, apoptosis, FoxO signaling pathway, platelet activation, neurotrophin signaling pathway and VEGF signaling pathway, which may be associated with the pathological of AIS. Three randomly selected circRNAs were successfully validated by qRT-PCR. The results show that hsa_circ_0005548 was significantly upregulated, while hsa_circ_0000607 and hsa_circ_0002465 were significantly downregulated in AIS. Furthermore, the AUC values for hsa_circ_005548, hsa_circ_0000607 and hsa_circ_0002465 were 0.51, 0.75 and 0.69, respectively, suggesting that hsa_circ_0000607 and hsa_circ_0002465 could be potential biomarkers for AIS. In addition, Bcl2 was predicted to be a direct target of miR-337-3p, and hsa_circRNA_0000607 was predicted to act as a sponge for miR-337-3p. Thus, hsa_circ_0000607 may be involved in AIS by regulating the miR-337-3p/Bcl2 axis. Collectively, our findings indicate that numerous dysregulated circRNAs may play pivotal functional roles in AIS and hsa_circ_0000607 may play a crucial role in the pathogenesis and progression of AIS by regulating the miR-337-3p/Bcl2 axis.

Dataset Information

Microarray and bioinformatics analysis of circular RNAs expression profile in traumatic lung injury.

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Microarray and bioinformatics analysis of circular RNAs expression profile in traumatic lung injury.

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