The Role of miRNA in Regulating the ZBP1-RIPK3-MLKL Pathway in Post-Influenza Inflammatory Responses
DOI:
https://doi.org/10.54097/2yv8qe04Keywords:
Z-DNA binding protein 1 (ZBP1); microRNA (miRNA); hsa-miR-361-3p; Influenza virus; Bioinformatics**.Abstract
Excessive inflammatory response triggered by influenza virus infection is a critical factor contributing to severe disease and mortality. Recent studies have revealed that necroptosis mediated by the ZBP1-RIPK3-MLKL signaling pathway plays a significant role in pulmonary immunopathological injury. MicroRNAs (miRNAs), as crucial post-transcriptional regulators, are pivotal in maintaining inflammatory balance; however, their regulatory mechanisms on the ZBP1 pathway during post-influenza inflammation remain unclear. In this study, bioinformatic analysis predicted miRNAs targeting ZBP1, and the human microRNA-361-3p (hsa-miR-361-3p) was identified as a novel candidate regulatory molecule via a dual-luciferase reporter assay. In A549 cells, hsa-miR-361-3p was confirmed to act on the 3'-untranslated region (3'-UTR) of ZBP1, reducing ZBP1 protein expression and the phosphorylation levels of its downstream effectors RIPK3 and MLKL. Overexpression of hsa-miR-361-3p significantly suppressed the expression of the inflammatory cytokines CXCL10 and IL-8 induced by Poly I:C. This study reveals that hsa-miR-361-3p may negatively regulate necroptosis and associated inflammatory responses by targeting ZBP1, providing new insights into the mechanisms underlying influenza virus-associated inflammatory storm.**
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