Regulation of response to nanopolystyrene by intestinal microRNA mir-35 in nematode Caenorhabditis elegans.

In nematode Caenorhabditis elegans, mir-35, a microRNA molecule, was involved in the control of response to nanopolystyrene. Exposure to nanopolystyrene (100 nm) could significantly increase the mir-35 expression. However, the underlying mechanism for this role of mir-35 remains largely unclear. Based on analysis of expression levels, phenotypes, and genetic interactions, we examined the underlying mechanism of intestinal mir-35 in regulating the response to nanopolystyrene. In nematodes, we here found that mir-35 acted in the intestine to regulate the response to nanopolystyrene. In the intestine, NDK-1, homolog of NM23-H1, was identified as the direct target of mir-35, suggesting that intestinal mir-35 regulated the response to nanopolystyrene by suppressing the NDK-1 function. Moreover, intestinal NDK-1 could regulate the response to nanopolystyrene by suppressing the function of FOXO transcriptional factor DAF-16 in the insulin signaling pathway. In nanopolystyrene exposed nematodes, kinase suppressors of Ras (KSR-1 and KSR-2) were further identified as downstream targets of intestinal NDK-1. Moreover, DAF-16 functioned with KSR-1 or KSR-2 in different pathways to regulate the response to nanopolystyrene. Therefore, we have identified an intestinal signaling cascade of mir-35-NDK-1-DAF-16/KSR-1/2 to be required for the control of response to nanopolystyrene. Our results provided an important molecular basis for intestinal response to nanopolystyrene in nematodes.