Liu Tingjun, Li Yuhan, Chen Shengjie, Wang Lulu, Liu Xiaolan, Yang Qingru, Wang Yan, Qiao Xiaorong, Tong Jing, Deng Xintao, Shao Shihe, Wang Hua, Shen Hongxing
Cardiothoracic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.
Front Microbiol. 2022 Oct 13;13:1012124. doi: 10.3389/fmicb.2022.1012124. eCollection 2022.
Coxsackievirus B3 (CVB3) was one of the most common pathogens to cause viral myocarditis. Circular RNAs as novel non-coding RNAs with a closed loop molecular structure have been confirmed to be involved in virus infectious diseases, but the function in CVB3 infection was not systematically studied. In this study, we identified that hsa_circ_0063331 (circDDX17) was drastically decreased after CVB3 infection by circRNA microarray. and , when cells or mice were infected with CVB3, the expression of circDDX17 was significantly reduced, as demonstrated by quantitative real-time PCR assays. Additionally, circDDX17 enhanced CVB3 replication by downregulating the expression of miR-1248 in HeLa and HL-1 cells, and miR-1248 regulated CVB3 replication through interacting with the gene coding for NOTCH Receptor 2 (NOTCH2), and NOTCH2 could upregulate methyltransferase-like protein 3 (METTL3). Taken together, this study suggested that circDDX17 promoted CVB3 replication and regulated NOTCH2 by targeting miR-1248 as a miRNAs sponge.
柯萨奇病毒B3（CVB3）是引起病毒性心肌炎最常见的病原体之一。环状RNA作为具有闭环分子结构的新型非编码RNA，已被证实参与病毒感染性疾病，但在CVB3感染中的作用尚未得到系统研究。在本研究中，我们通过环状RNA微阵列鉴定出hsa_circ_0063331（circDDX17）在CVB3感染后显著降低。此外，当细胞或小鼠感染CVB3时，定量实时PCR分析表明circDDX17的表达显著降低。此外，circDDX17通过下调HeLa和HL-1细胞中miR-1248的表达来增强CVB3复制，miR-1248通过与编码NOTCH受体2（NOTCH2）的基因相互作用来调节CVB3复制，而NOTCH2可以上调甲基转移酶样蛋白3（METTL3）。综上所述，本研究表明circDDX17作为一种miRNA海绵，通过靶向miR-1248促进CVB3复制并调节NOTCH2。
