Exposure to graphene oxide (GO) induced some dysregulated microRNAs (miRNAs), such as the increase in
mir-247, in nematode Caenorhabditis elegans. We here further identified
goa-1 encoding a Go and
pkc-1 encoding a serine/threonine protein kinase as the targets of neuronal
mir-247 in the regulation of GO toxicity. GO exposure increased the expressions of both GOA-1 and PKC-1. Mutation of
goa-1 or
pkc-1 induced a susceptibility to GO toxicity, and suppressed the resistance of
mir-247 mutant to GO toxicity. GOA-1 and PKC-1 could also act in the neurons to regulate the GO toxicity, and neuronal overexpression of
mir-247 could not affect the resistance of nematodes overexpressing neuronal
goa-1 or
pkc-1 lacking 3'-UTR to GO toxicity. In the neurons, GOA-1 acted upstream of diacylglycerol kinase/DGK-1 and PKC-1 to regulate the GO toxicity. Moreover, DGK-1 and GOA-1 functioned synergistically in the regulation of GO toxicity. Our results highlight the crucial role of neuronal Go signaling in response to GO in nematodes.