A circular RNA circ_0000115 in response to graphene oxide in nematodes

Circular RNAs (circRNAs) play important roles in regulating various biological processes; however, their roles in regulating the toxicity of engineered nanomaterials (ENMs) are still unclear. Based on Illumina HiSeq2500 sequencing, we here identified 43 dysregulated circRNAs in graphene oxide (GO) (1 mg L(−1)) exposed nematodes. Five of these candidate circRNAs could be further dysregulated by GO exposure in the range of μg L(−1). Using the RNA interference (RNAi) technique, we found that the alteration in expressions of circ_0000115, circ_0000247, and circ_0000665 mediated a protective response to GO exposure; however, the alteration in expressions of circ_0000201 and circ_0000308 mediated the toxicity induction of GO. In nematodes, the circ_0000115 acted in certain tissues (intestine and neurons) to regulate GO toxicity. Moreover, an intermediate filament protein IFC-2 required for intestinal development was identified as a target of circ_0000115 in regulating the GO toxicity. In the intestine, intestinal IFC-2 acted further upstream of FOXO transcriptional factor DAF-16 in the insulin signaling pathway to regulate the GO toxicity. Therefore, intestinal circ_0000115 in the signaling cascade of circ_0000115-IFC-2-DAF-16 regulates the GO toxicity by modulating the function of IFC-2.