Enterovirus 71 induces pyroptosis of human neuroblastoma SH-SY5Y cells through miR-146a/ CXCR4 axis

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. •EV71 increases caspase-1/NLRP3 dependent pyroptosis of SH-SY5Y cells through miRNA-146a/CXCR4 axis.•A novel miRNA-mRNA mechanism of pyroptosis in EV71-infected human neuroblastoma cells has been explored.•As an inflammatory PCD, pyroptosis accounts for part of the pathogenesis in the nervous system injury in EV71 caused HFMD.