Identification of potential circRNA-miRNA-mRNA regulatory networks in response to graphene quantum dots in microglia by microarray analysis
Identification of potential circRNA-miRNA-mRNA regulatory networks in response to graphene quantum dots in microglia by microarray analysis
复制标题
通过微阵列分析鉴定小胶质细胞中响应石墨烯量子点的潜在 circRNA-miRNA-mRNA 调控网络
DOI：
10.1016/j.ecoenv.2020.111672
复制
发表时间：
2021
影响因子：
6.8
通讯作者：
Tang Meng
中科院分区：
文献类型：
--
作者：
Wu Tianshu;Li Yimeng;Liang Xue;Liu Xi;Tang Meng
随着石墨烯量子点（GQD）在生物医学和神经科学领域的应用不断增加，评估GQD对中枢神经系统（CNS）可能产生的不利影响非常重要，但其潜在的毒性机制仍不清楚。在这项研究中，我们通过RNA微阵列的综合分析，评估了氮掺杂GQD（N-GQD）和氨基功能化GQD（A-GQD）的环状RNA（circRNA）破坏小胶质细胞活力和细胞结构相关的分子机制。在用 25 µg/mL N-GQD、100 µg/mL N-GQD 和 100 µg/mL A-GQD 处理的 BV2 小胶质细胞中进行差异表达 circRNA (DEcircRNA)-miRNA-差异表达 mRNA (DEmRNA) 调控网络。在此基础上，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circRNA间接介导的信号通路。发现了一些在N-GQDs或两种GQDs的神经毒性中可能发挥不可或缺作用的途径。低剂量的N-GQDs暴露主要诱导小胶质细胞的炎症作用，而高剂量的N-GQDs和A-GQDs暴露均影响嗅觉转导和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两种GQD的神经毒性产生不同的影响。这些 circRNA 可能是 GQD 神经毒性的毒性生物标志物或保护靶点。更重要的是，他们强调了在石墨烯基纳米材料生物安全评估中通过表观遗传学方法全面分析潜在分子机制的必要性。
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.