Identification and validation of key regulating circRNAs in Immune Thrombocytopenia by circRNAs sequencing

IF 1 Q4 GENETICS & HEREDITY Gene Reports Pub Date : 2024-07-29 DOI:10.1016/j.genrep.2024.101992
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Abstract

Dysfunction of T cells is a causative factor in Immune Thrombocytopenia (ITP), an autoimmune disorder. Circular RNAs (circRNAs), which have been associated with the pathophysiology of various immunological conditions, are of particular interest. Our study aimed to identify pivotal regulatory circRNAs within the peripheral T cells of ITP patients. We utilized circRNA sequencing to discern differences in circRNA expression between the ITP cohort and healthy controls. We identified 606 upregulated and 719 downregulated circRNAs. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to scrutinize the parent genes of these differentially expressed circRNAs, revealing their significant involvement in metabolic processes and T cell receptor signaling pathways. Following a rigorous selection process that included DEG analysis, KEGG, and GO pathways analysis, along with an assessment of the potential roles of their parent genes, five top differentially expressed circRNAs were subjected to further validation via quantitative Polymerase Chain Reaction (RT-qPCR). Specifically, in the peripheral T cells of ITP patients, hsa_circ_0008866 (TAOK1), hsa_circ_0006856 (MAP3K5), and hsa_circ_0007444 (RHOBTB3) emerged as key regulatory circRNAs. The potential miRNA targets of these circRNAs were predicted employing miRanda, RNAhybrid, and TargetScan algorithms.

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通过 circRNAs 测序鉴定和验证免疫性血小板减少症的关键调控 circRNAs
T 细胞功能障碍是免疫性血小板减少症(ITP)这一自身免疫性疾病的致病因素。环状 RNA(circRNA)与各种免疫疾病的病理生理学有关,因此特别引人关注。我们的研究旨在确定ITP患者外周T细胞中的关键调控circRNA。我们利用 circRNA 测序技术来鉴别 ITP 组群与健康对照组之间 circRNA 表达的差异。我们发现了 606 个上调和 719 个下调的 circRNA。我们随后进行了基因本体(GO)和京都基因组百科全书(KEGG)富集分析,仔细研究了这些不同表达的 circRNA 的母基因,发现它们在新陈代谢过程和 T 细胞受体信号通路中有重要参与。经过包括 DEG 分析、KEGG 和 GO 通路分析在内的严格筛选过程,以及对其母体基因潜在作用的评估,五种最高差异表达的 circRNA 通过定量聚合酶链反应(RT-qPCR)得到了进一步验证。具体来说,在ITP患者的外周T细胞中,hsa_circ_0008866(TAOK1)、hsa_circ_0006856(MAP3K5)和hsa_circ_0007444(RHOBTB3)成为关键的调控circRNA。利用 miRanda、RNAhybrid 和 TargetScan 算法预测了这些 circRNA 的潜在 miRNA 靶点。
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来源期刊
Gene Reports
Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.30
自引率
7.70%
发文量
246
审稿时长
49 days
期刊介绍: Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.
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