Along with the increasing application of graphene quantum dots (GQDs) in the fields of biomedicine and neuroscience, it is important to assess the probably adverse effects of GQDs in the central nervous system (CNS) but their underlying toxic mechanisms is still unclear. In this study, we evaluate the molecular mechanisms associated with circular RNAs (circRNAs) of nitrogen-doped GQDs (N-GQDs) and amino-functionalized GQDs (A-GQDs) damaging the cell viability and cellular structure in microglia by an integrative analysis of RNA microarray. The differentially expressed circRNA (DEcircRNAs)-miRNA- differentially expressed mRNA (DEmRNAs) regulatory networks were conducted in BV2 microglial cells treated with 25 µg/mL N-GQDs, 100 µg/mL N-GQDs and 100 µg/mL A-GQDs. Based on that, the protein-coding genes in each ceRNA network were collected to do bio-functional analysis to evaluate signaling pathways that were indirectly mediated by circRNAs. Some pathways that could play indispensable roles in the neurotoxicity of N-GQDs or both two kinds of GQDs were found. Low-dosed N-GQDs exposure mainly induced inflammatory action in microglia, while high-dosed N-GQDs and A-GQDs exposure both affect olfactory transduction and GABAergic synapse. Meanwhile, several classical signaling pathways, including mTOR, ErbB and MAPK, could make diverse contributions to the neurotoxicity of both two kinds of GQDs. These circRNAs could be toxic biomarkers or protective targets in neurotoxicity of GQDs. More importantly, they emphasized the necessity of comprehensive analysis of latent molecular mechanisms through epigenetics approaches in biosafety assessment of graphene-based nanomaterials.

随着石墨烯量子点（GQD）在生物医学和神经科学领域中的越来越多的应用，评估GQD在中枢神经系统（CNS）中可能产生的不利影响非常重要，但它们的潜在毒性机制仍不清楚。在这项研究中，我们通过对小胶质细胞的活力和细胞结构进行破坏性分析，评估了与氮掺杂GQD（N-GQDs）和氨基官能化GQD（A-GQDs）的环状RNA（circRNA）相关的分子机制。 RNA微阵列。在用25 µg / mL N-GQD，100 µg / mL N-GQD和100 µg / mL A-GQD处理过的BV2小胶质细胞中进行了差异表达的circRNA（DEcircRNAs）-miRNA-差异表达的mRNA（DEmRNAs）调控网络。基于此，收集每个ceRNA网络中的蛋白质编码基因进行生物功能分析，以评估由circRNA间接介导的信号通路。发现了一些可能在N-GQD或两种GQD的神经毒性中起不可缺少的作用的途径。低剂量的N-GQDs暴露主要引起小胶质细胞的炎症反应，而高剂量的N-GQDs和A-GQDs暴露都影响嗅觉转导和GABA能突触。同时，包括mTOR，ErbB和MAPK在内的几种经典信号通路可能对这两种GQD的神经毒性做出不同的贡献。这些circRNAs可能是GQD神经毒性的有毒生物标志物或保护性靶标。更重要的是，