miR-200b Regulates Cellular Proliferation and Inflammatory Responses by Targeting Dual-Specificity Phosphatase 1 in Lower Vertebrates, Sciaenops ocellatus.

DUSP1 is a representative member of the dual-specificity protein phosphatase family known to dephosphorylate MAPK family members and is crucial in the biosynthesis of proinflammatory cytokines. In mammals, DUSP1 is also involved in various functions including proliferation, differentiation, and apoptosis. However, little is known about the function and mechanism of DUSP1 regulating antibacterial immune response in teleost. MicroRNAs (miRNAs) have emerged as essential regulators with profound effects on immune and inflammation responses, but in teleost, the miRNA-mediated regulatory networks at different levels of signaling pathways remain largely unknown. In this study, the regulatory mechanism of the miR-200b-DUSP1-mediated inflammatory responses in teleost was addressed. We found that the expression of DUSP1 could be significantly regulated by Vibrio harveyi and lipopolysaccharide in Sciaenops ocellatus. Overexpression of DUSP1 resulted in the suppression of proinflammatory cytokine expression and cell proliferation, indicating that DUSP1 acts as a negative regulator in inflammatory responses. Furthermore, we found that miR-200b is a post-transcriptional regulator of DUSP1 that is highly expressed upon bacterial infections. Bacteria-induced miR-200b promoted cell proliferation and inflammatory responses through targeting S. ocellatus DUSP1 and increasing NF-κB signaling pathway. These results suggest that miR-200b plays a key role in promoting antibacterial immune responses through directly targeting the immune regulatory molecule DUSP1, which will greatly enrich the networks of host-pathogen interactions in lower vertebrates.