Dysregulated mir-354 enhanced the protective response to nanopolystyrene by affecting the activity of TGF-β signaling pathway in nematode Caenorhabditis elegans

Abstract The microRNA molecule mir-354 was required for the control of nanopolystyrene toxicity in nematode Caenorhabditis elegans. Exposure to nanopolystyren (100 nm) increased the mir-354 expression; however, the underlying mechanism for this role remains largely unknown. We here further determined the molecular basis of mir-354 in regulating the response to nanopolystyrene. Tissue-specific activity analysis indicated that mir-354 acted in the intestine to regulate the toxicity of nanopolystyrene. During the control of nanopolystyrene toxicity, DAF-3, a transcriptional factor in DAF-7-mediated TGF-β signaling pathway, was identified as the downstream target of intestinal mir-354. In the DAF-7-mediated TGF-β signaling pathway, an intestinal signaling cascade of DAF-1-DAF-8-DAF-3/DAF-5 was activated by neuronal TGF-β ligand DAF-7 in nanopolystyrene exposed nematodes. In this intestinal signaling cascade, DAF-1-DAF-8 regulated the response to nanopolystyrene by inhibiting the function of downstream two transcriptional factors of DAF-3 and DAF-5. Moreover, intestinal DAF-3 and DAF-5 could further regulate the response to nanopolystyrene by suppressing the function of nuclear hormone receptor DAF-12. Therefore, in nanopolystyrene exposed nematodes, the observed dysregulation of mir-354 enhanced the protective response to nanopolystyrene by affecting the activity of DAF-7-mediated TGF-β signaling pathway. Our data highlights the important role of TGF-β signaling pathway-mediated protective response to nanoplastic exposure in organisms.