The widespread use of graphene oxide-silver nanoparticle nanocomposites (GO-AgNPs) in biomedical sciences is increasing the chances of human and animal exposure to its chronic non-toxic doses. Exposure to AgNPs-related nanomaterials may result in the negative effect on the dam, fetus and offspring. However, there are only little available information for profound understanding of the epigenetic alteration in the cells and animals caused by low-dose chronic exposure of GO-AgNPs. The present study investigated the effect of 0.5 μg/mL GO-AgNPs for 10 weeks on the differential expression of circular RNAs (circRNAs) in caprine fetal fibroblast cells (CFFCs), and this dose of GO-AgNPs did not affect cell viability and ROS level. We predicted the functions of those differentially expressed (DE) circRNAs in CFFCs by bioinformatics analysis. Furthermore, we validated the expression of ten DE circRNAs using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) to ensure the reliability of the sequencing data. Our results showed that the DE circRNAs may potentially regulate the GO-AgNPs-inducing epigenetic toxicity through a regulatory network consisted of circRNAs, miRNAs and messenger RNAs (mRNAs). Therefore, the epigenetics toxicity is essential to assess the biosafety level of GO-AgNPs.

中文翻译：

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暴露于长期非细胞毒性剂量的氧化石墨烯-银纳米粒子纳米复合材料的山羊胎儿成纤维细胞中环状 RNA 表达模式的鉴定

氧化石墨烯-银纳米粒子纳米复合材料 (GO-AgNPs) 在生物医学科学中的广泛使用增加了人类和动物接触其慢性无毒剂量的机会。接触 AgNPs 相关的纳米材料可能会对母体、胎儿和后代产生负面影响。然而，只有很少的可用信息可以深入了解由低剂量长期暴露于 GO-AgNPs 引起的细胞和动物的表观遗传改变。本研究调查了 0.5 μg/mL GO-AgNPs 10 周对山羊胎儿成纤维细胞 (CFFCs) 中环状 RNA (circRNAs) 差异表达的影响，并且该剂量的 GO-AgNPs 不影响细胞活力和 ROS等级。我们通过生物信息学分析预测了 CFFC 中那些差异表达 (DE) circRNA 的功能。此外，我们使用定量实时逆转录-聚合酶链反应 (qRT-PCR) 验证了 10 个 DE circRNA 的表达，以确保测序数据的可靠性。我们的结果表明，DE circRNAs 可能通过由 circRNAs、miRNAs 和信使 RNAs (mRNAs) 组成的调控网络潜在地调控 GO-AgNPs 诱导的表观遗传毒性。因此，表观遗传学毒性对于评估 GO-AgNPs 的生物安全水平至关重要。