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Circular RNA expression alteration and bioinformatics analysis in patients with acute cerebral infarction injury.

ABSTRACT: In recent years, a steady increase has been detected in the incidence of acute cerebral infarction (ACI). ACI is caused by blood flow disruption, leading to high disability and mortality rates. Understanding the underlying molecular mechanisms is critical toward developing effective therapeutic approaches. Circular RNAs (circRNAs) are an important class of non-coding RNAs, which have been implicated in several molecular pathways, and their dysregulation has been described in several disease conditions. Here, we set out to explore the possible regulatory role of circRNAs in ischemic stroke and study their molecular function in disease. First, we applied high-throughput sequencing techniques to identify the differential changes of plasma circRNAs expression in patients with acute cerebral infarction. Next, we used GO and KEGG pathway analysis to predict the function of differentially expressed circRNAs. Moreover, we have assessed the possible interaction between the identified differentially expressed circRNAs and miRNAs. Finally, we have selected and validated five downregulated circRNAs by RT-qPCR. Together, the results of this study provide evidence that circRNAs are potential biomarkers for early diagnosis of cerebral infarction and have to be considered as targets for drug treatment.

SUBMITTER: Hu XL

PROVIDER: S-EPMC8810197 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Circular RNA expression alteration and bioinformatics analysis in patients with acute cerebral infarction injury.

Hu Xiao-Lei XL Su Qian Q Meng de-Long DL Ren Yuan-Shui YS Su Zhi-Qiang ZQ

Bioengineered 20211201 2

In recent years, a steady increase has been detected in the incidence of acute cerebral infarction (ACI). ACI is caused by blood flow disruption, leading to high disability and mortality rates. Understanding the underlying molecular mechanisms is critical toward developing effective therapeutic approaches. Circular RNAs (circRNAs) are an important class of non-coding RNAs, which have been implicated in several molecular pathways, and their dysregulation has been described in several disease cond ...[more]

PMID: 34873976

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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:Previous studies pointed out that a variety of microRNAs (miRNAs) are involved in the pathogenesis of neonatal acute respiratory distress syndrome (NARDS) and play different roles in the pathological process. However, there have been few studies reporting the connection between circular RNA (circRNA) and NARDS, so the expression profile of circRNAs in newborns with acute respiratory distress syndrome remains largely unknown. In the present study, 10 samples obtained from remaining clinical blood samples of newborns hospitalized in a neonatal ward of the First Affiliated Hospital of Nanjing Medical University from January 2020 to October 2020 were divided into the "NARDS" group and "non-NARDS" group according to the Montelux standard and then were analyzed in microarray, and 10 other samples collected from the same place and from January 1, 2021 to August 31, 2021, were used to do RT-qPCR experiment. circRNA expression profiles, in which 741 circRNAs were downregulated and 588 were upregulated, were screened with circRNA high-throughput sequencing. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of parent genes of the differentially expressed circRNAs revealed that these circRNAs may be related to the process of protein synthesis and metabolism in NARDS. Moreover, five circRNAs-hsa_circ_0058495, hsa_circ_0000367, hsa_circ_0005389, hsa_circ_0059571, and hsa_circ_0006608-were selected randomly among the top 10 circRNAs of the downregulated or upregulated expression profiles. Then, bioinformatics tools were used to predict correlative miRNA and its target genes, which were also subjected to the same bioinformatics analysis for further study. The top 30 enriched KEGG pathway analyses of the 125 target genes suggested that these target genes are widely involved in the synthesis and secretion of endocrine hormones, and the top 30 enriched GO terms based on the 125 target genes are also focused on the protein and DNA processing. Thus, the present results show that circRNAs could promote the inflammation of NARDS which may provide a new therapeutic direction and it can be used as molecular markers for early diagnosis of NARDS, but further molecular biology verification is needed to define the specific role of differentially expressed circRNAs in NARDS.

Project description:IntroductionNeurons transport mRNA and translational machinery to axons for local translation. After spinal cord injury (SCI), de novo translation is assumed to enable neurorepair. Knowledge of the identity of axonal mRNAs that participate in neurorepair after SCI is limited. We sought to identify and understand how axonal RNAs play a role in axonal regeneration.MethodsWe obtained preparations enriched in axonal mRNAs from control and SCI rats by digesting spinal cord tissue with cold-active protease (CAP). The digested samples were then centrifuged to obtain a supernatant that was used to identify mRNA expression. We identified differentially expressed genes (DEGS) after SCI and mapped them to various biological processes. We validated the DEGs by RT-qPCR and RNA-scope.ResultsThe supernatant fraction was highly enriched for mRNA from axons. Using Gene Ontology, the second most significant pathway for all DEGs was axonogenesis. Among the DEGs was Rims2, which is predominately a circular RNA (circRNA) in the CNS. We show that Rims2 RNA within spinal cord axons is circular. We found an additional 200 putative circRNAs in the axonal-enriched fraction. Knockdown in primary rat cortical neurons of the RNA editing enzyme ADAR1, which inhibits formation of circRNAs, significantly increased axonal outgrowth and increased the expression of circRims2. Using Rims2 as a prototype we used Circular RNA Interactome to predict miRNAs that bind to circRims2 also bind to the 3'UTR of GAP-43, PTEN or CREB1, all known regulators of axonal outgrowth. Axonally-translated GAP-43 supports axonal elongation and we detect GAP-43 mRNA in the rat axons by RNAscope.DiscussionBy enriching for axonal RNA, we detect SCI induced DEGs, including circRNA such as Rims2. Ablation of ADAR1, the enzyme that regulates circRNA formation, promotes axonal outgrowth of cortical neurons. We developed a pathway model using Circular RNA Interactome that indicates that Rims2 through miRNAs can regulate the axonal translation GAP-43 to regulate axonal regeneration. We conclude that axonal regulatory pathways will play a role in neurorepair.

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Circular RNA expression alteration and bioinformatics analysis in patients with acute cerebral infarction injury.

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Circular RNA expression alteration and bioinformatics analysis in patients with acute cerebral infarction injury.

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