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TDCIPP 暴露诱导 PC12 细胞 circRNA 表达谱的变化可能通过 Traf2 基因调节下游 NF-κB 通路。

Changes in the circRNA expression profile of PC12 cells induced by TDCIPP exposure may regulate the downstream NF-κB pathway via the Traf2 gene.

机构信息

School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, 300070, China; Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, 300050, China.

Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, 300050, China.

出版信息

Chemosphere. 2020 Sep;254:126834. doi: 10.1016/j.chemosphere.2020.126834. Epub 2020 Apr 21.

Abstract

As a commonly used organophosphorus flame retardant (OPFR), tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) has become an environmental pollutant. Studies have shown that TDCIPP exposure has many toxic effects, such as neurotoxicity, reproductive development toxicity and endocrine disturbance. CircRNAs are circular noncoding RNAs that have been found to play important roles in the occurrence of a variety of diseases. However, it is unclear whether circRNAs play a role in the cytotoxicity induced by TDCIPP exposure. In this study, we analysed the circRNA microarray results of a control group and a TDCIPP exposure group of PC12 cells and detected 3432 differentially expressed circRNAs (P < 0.05), of which 1682 were upregulated and 1750 were downregulated in the TDCIPP-exposure group. The expression levels of 2 upregulated and 3 downregulated circRNAs were verified by real-time quantitative PCR, and the results were consistent with the microarray results. Then, ceRNA analysis was performed on several kinds of circRNAs to predict the possible binding miRNAs and binding sites. The target genes were analysed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Through predictive analysis, it was found that rno_circRNA_013845, rno-miR-361-3p, and rno-miR-702-3p may be involved in the regulation of Traf2 expression, thereby affecting the expression of the downstream NF-κB signalling pathway and causing apoptosis.

摘要

作为一种常用的有机磷阻燃剂(OPFR),磷酸三(1,3-二氯-2-丙基)酯(TDCIPP)已成为一种环境污染物。研究表明,TDCIPP 暴露具有许多毒性作用,如神经毒性、生殖发育毒性和内分泌干扰。CircRNAs 是环状非编码 RNA,已被发现在多种疾病的发生中发挥重要作用。然而,CircRNAs 是否在 TDCIPP 暴露诱导的细胞毒性中发挥作用尚不清楚。在这项研究中,我们分析了对照组和 TDCIPP 暴露组 PC12 细胞的 circRNA 微阵列结果,检测到 3432 个差异表达的 circRNAs(P<0.05),其中 1682 个在 TDCIPP 暴露组中上调,1750 个下调。通过实时定量 PCR 验证了 2 个上调和 3 个下调的 circRNAs 的表达水平,结果与微阵列结果一致。然后,对几种 circRNAs 进行 ceRNA 分析,预测可能的结合 miRNA 和结合位点。通过京都基因与基因组百科全书(KEGG)通路分析对靶基因进行分析。通过预测分析,发现 rno_circRNA_013845、rno-miR-361-3p 和 rno-miR-702-3p 可能参与了 Traf2 表达的调节,从而影响下游 NF-κB 信号通路的表达,导致细胞凋亡。

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