Abstract

Graphene quantum dots (GQDs) have a bright prospect to be applied in the field of biomedicine and have been reported to be associated with adverse events in the central nervous system, but it is still not clear of their underlying mechanisms. After observing the adverse effects, including decreased cell viability, DNA damage, and impairments of intracellular structure, caused by nitrogen-doped GQDs (N-GQDs) and amino-functionalized GQDs (A-GQDs), a microarray analysis was conducted to comprehensively gain the information on the neurotoxic molecular mechanisms of N-GQDs and A-GQDs, which is associated with long non-coding RNAs (lncRNAs) proposed to participate into multiple neuronal disorders. The exclusive differentially expressed lncRNA (DElncRNA) transcripts by N-GQDs at different exposure doses or A-GQDs were collected to do the functional analysis in order to find the pathways of GQDs causing toxic effects in microglia under different circumstances. Meanwhile, the findings suggested the pathways in which the shared DElncRNAs involved could play indispensable roles in neurotoxicity of N-GQDs and GQDs no matter with what surface modification, such as wnt, calcium and MAPK signalling pathways. Moreover, protein-coding genes cis- and/or trans-regulated by these DElncRNAs or transcriptional factors (TFs) interacted with DElncRNAs were detected, like sox4, hoxc9 and pou3f1, in this study. Therefore, lncRNAs identified by the omic approach could be useful candidate biomarkers or protective targets in neurotoxicity of GQDs, which indicated the pivotal role of post-transcriptional regulation in toxicity of graphene-based nanomaterials.