Bioinformatics and Screening of a Circular RNA-microRNA-mRNA Regulatory Network Induced by Coxsackievirus Group B5 in Human Rhabdomyosarcoma Cells.

Bioinformatics and Screening of a Circular RNA-microRNA-mRNA Regulatory Network Induced by Coxsackievirus Group B5 in Human Rhabdomyosarcoma Cells.
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柯萨奇病毒 B5 组在人横纹肌肉瘤细胞中诱导的环状 RNA-microRNA-mRNA 调控网络的生物信息学和筛选

DOI:
10.3390/ijms23094628
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发表时间:
2022-04-22
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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--
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由柯萨奇病毒B5组(Coxsackievirus Group B5,CVB 5)引起的手足口病(Hand,Foot and Mouth Disease,HFMD)是人类婴儿和儿童最常见的疱疹性疾病之一。CVB 5的发病机制尚不清楚。Circular RNA(CircRNA)作为一种新型的非编码RNA,在许多物种的致病过程中发挥着重要作用,但其在CVB 5感染过程中的功能尚不清楚。在本研究中,我们使用RNA测序技术在CVB 5感染和模拟感染的人横纹肌肉瘤细胞(从临床标本中分离的CVB 5病毒)中研究了circRNA的表达谱。此外,通过RT-qPCR验证了几种差异表达的circRNA。此外,构建并验证了与circRNA-miRNA-mRNA相互作用网络相关的天然免疫应答。在CVB 5感染和对照组的不同基因组位置共鉴定了5461个circRNA,其中235个差异表达。基因本体论(GO)和京都基因和基因组百科全书(KEGG)富集分析表明,差异表达的circRNA主要参与ErbB、TNF和先天免疫相关的特异性信号通路。我们进一步预测novel_circ_0002006可能通过IFN-I途径作为miR-152- 3 p的分子海绵来抑制CVB 5的复制,novel_circ_0001066可能通过NF-κB途径作为miR-29 B-3 p的分子海绵来抑制CVB 5的复制。这些发现将有助于阐明circRNA在CVB 5相关HFMD进展中的生物学功能,并确定该疾病的潜在生物标志物和治疗靶点。
Hand, foot and mouth disease (HFMD) caused by Coxsackievirus Group B5 (CVB5) is one of the most common herpetic diseases in human infants and children. The pathogenesis of CVB5 remains unknown. Circular RNAs (CircRNAs), as novel noncoding RNAs, have been shown to play a key role in many pathogenic processes in different species; however, their functions during the process of CVB5 infection remain unclear. In the present study, we investigated the expression profiles of circRNAs using RNA sequencing technology in CVB5-infected and mock-infected human rhabdomyosarcoma cells (CVB5 virus that had been isolated from clinical specimens). In addition, several differentially expressed circRNAs were validated by RT-qPCR. Moreover, the innate immune responses related to circRNA-miRNA-mRNA interaction networks were constructed and verified. A total of 5461 circRNAs were identified at different genomic locations in CVB5 infections and controls, of which 235 were differentially expressed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis demonstrated that the differentially expressed circRNAs were principally involved in specific signaling pathways related to ErbB, TNF, and innate immunity. We further predicted that novel_circ_0002006 might act as a molecular sponge for miR-152-3p through the IFN-I pathway to inhibit CVB5 replication, and that novel_circ_0001066 might act as a molecular sponge for miR-29b-3p via the NF-κB pathway and for the inhibition of CVB5 replication. These findings will help to elucidate the biological functions of circRNAs in the progression of CVB5-related HFMD and identify prospective biomarkers and therapeutic targets for this disease.
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