肠道病毒71型通过miR-146a/CXCR4轴诱导人神经母细胞瘤SH-SY5Y细胞焦亡。
Enterovirus 71 induces pyroptosis of human neuroblastoma SH-SY5Y cells through miR-146a/ CXCR4 axis.
作者信息
Guo Hengzhong, Zhu Yangyang, Zou Yu, Li Chaozhi, Wang Ya, De Gejing, Lu Lili
机构信息
Hubei Province Key Laboratory of Occupational Hazard Identification and Control, College of Medicine, Wuhan University of Science and Technology, 430065, Wuhan, Hubei, PR China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, 100700, Beijing, PR China.
出版信息
Heliyon. 2023 Mar 29;9(4):e15014. doi: 10.1016/j.heliyon.2023.e15014. eCollection 2023 Apr.
Enterovirus 71 (EV71) is a predominant causative pathogen of hand-foot-and-mouth disease (HFMD) in children. Compared with other HFMD-associated viruses, EV71 tends to induce more severe neurological complications and even death. However, the detailed mechanism of EV71 causes nervous system disorder is still unclear. In this study, we found that EV71 induced the GSDMD/NLRP3-mediated pyroptosis of SH-SY5Y cells through up-regulated miR-146a. Through bioinformatic analysis, we identified C-X-C chemokine receptor type 4 (CXCR4) as the potential target of miR-146a. We noticed that the expression of CXCR4 was regulated by miR-146a during EV71 infection. Moreover, our results show that over-expression of CXCR4 attenuated EV71-induced pyroptosis of SY-SY5Y cells. These results reveal a previously unrecognized mechanism in which EV71 induces nervous system cells damage through regulating miR-146a/CXCR4 mediated pyroptosis.
肠道病毒71型（EV71）是儿童手足口病（HFMD）的主要致病病原体。与其他手足口病相关病毒相比，EV71更容易引发更严重的神经系统并发症甚至死亡。然而，EV71导致神经系统紊乱的详细机制仍不清楚。在本研究中，我们发现EV71通过上调miR-146a诱导SH-SY5Y细胞发生GSDMD/NLRP3介导的细胞焦亡。通过生物信息学分析，我们确定C-X-C趋化因子受体4型（CXCR4）为miR-146a的潜在靶点。我们注意到在EV71感染期间，CXCR4的表达受miR-146a调控。此外，我们的结果表明，CXCR4的过表达减弱了EV71诱导的SY-SY5Y细胞焦亡。这些结果揭示了一种以前未被认识的机制，即EV71通过调节miR-146a/CXCR4介导的细胞焦亡诱导神经细胞损伤。
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