Mechanism Of LncRNAs Regulating Graphene Oxide In Vivo Toxicity In Caenorhabditis Elegans

Due to its excellent biocompatibility and physiochemical properties, graphene oxide (GO), a novel member of carbon nanomaterials, has shown great potential in many applications. The biosafety and its protential harm to the human health by environmental exposure and the mechanism of toxicity have also caused extensive concerns. Caenorhabditis elegans is a well-established model for toxicology testing in biomedical and environmental fields. Previous studies have revealed the molecular mechanism of regulating GO in vivo toxicity both in mRNA and miRNA levels. Long noncoding RNAs (lncRNAs) are defined as noncoding RNAs having at least 200 nucleotides and can potentially regulate various biological processes. However, the roles of lncRNAs in regulating behavior of engineered nanomaterials (ENMs) are still unclear so far.By using Hiseq 2000 sequencing technique, we performed genome-wide screen to identify lncRNAs involved in the control of toxicity of graphene oxide (GO) in in vivo C.elegans assay system. Hiseq 2000 sequencing followed by quantitative analysis identified only 34 dysregulated lncRNAs in GO exposed nematodes. A lncRNAs-miRNAs network possibly involved in the control of GO toxicity was further raised. Bioinformatics analysis implies the biological processes and signaling pathways mediated by candidate lncRNAs involved in the control of GO toxicity.Moreover, we indentified the shared lncRNAs which are linc-37 and linc-14 based molecular regulation basis for chemical surface modifications (PEG modification and FBS coating) and/or genetic mutations (clk-1 and isp-1 gene mutations) in reducing GO toxicity.We further provide direct evidence to prove the function of linc-37 encoding the shared lncRNAs based molecular mechanisms for chemical surface modifications and genetic mutations in enhancing GO toxicity. linc-37 might be under the control of transcriptional factor FOXO/DAF-16 to regulate GO toxicity.Our whole-genome identification and functional analysis of lncRNAs provide highlights on the lncRNAs based molecular mechanisms for behavior of ENMs in organisms.