A circular RNA circ_0000115 in response to graphene oxide in nematodes.

A circular RNA circ_0000115 in response to graphene oxide in nematodes.
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线虫中响应氧化石墨烯的环状 RNA circ_0000115

DOI:
10.1039/c9ra00997c
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发表时间:
2019-04-30
期刊:
影响因子:
3.9
通讯作者:
--
中科院分区:
化学3区
文献类型:
--
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环状RNA(circRNA)在调节各种生物过程中发挥重要作用;然而,它们在调节工程纳米材料(ENMs)毒性中的作用仍不清楚。基于Illumina HiSeq 2500测序,我们在氧化石墨烯(GO)(1 mg L−1)暴露的线虫中鉴定了43种失调的circRNA。这些候选circRNA中的五种可能会在μg L−1范围内的GO暴露中进一步失调。使用RNA干扰(RNAi)技术,我们发现,在表达的变化,circ_0000115,circ_0000247,和circ_0000665介导的保护性反应,以GO暴露;然而,在表达的变化,circ_0000201和circ_0000308介导的毒性诱导GO。在线虫中,circ_0000115在某些组织(肠和神经元)中起作用以调节GO毒性。此外,肠发育所需的中间丝蛋白IFC-2被鉴定为circ_0000115调节GO毒性的靶标。在肠道中,肠道IFC-2在胰岛素信号传导途径中的FOXO转录因子β-16的上游进一步发挥作用,以调节GO毒性。因此,在circ_0000115-IFC-2-IFN-16的信号级联中,肠circ_0000115通过调节IFC-2的功能来调节GO毒性。
Circular RNAs (circRNAs) play important roles in regulating various biological processes; however, their roles in regulating the toxicity of engineered nanomaterials (ENMs) are still unclear. Based on Illumina HiSeq2500 sequencing, we here identified 43 dysregulated circRNAs in graphene oxide (GO) (1 mg L−1) exposed nematodes. Five of these candidate circRNAs could be further dysregulated by GO exposure in the range of μg L−1. Using the RNA interference (RNAi) technique, we found that the alteration in expressions of circ_0000115, circ_0000247, and circ_0000665 mediated a protective response to GO exposure; however, the alteration in expressions of circ_0000201 and circ_0000308 mediated the toxicity induction of GO. In nematodes, the circ_0000115 acted in certain tissues (intestine and neurons) to regulate GO toxicity. Moreover, an intermediate filament protein IFC-2 required for intestinal development was identified as a target of circ_0000115 in regulating the GO toxicity. In the intestine, intestinal IFC-2 acted further upstream of FOXO transcriptional factor DAF-16 in the insulin signaling pathway to regulate the GO toxicity. Therefore, intestinal circ_0000115 in the signaling cascade of circ_0000115-IFC-2-DAF-16 regulates the GO toxicity by modulating the function of IFC-2.
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