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鉴定氧化钕纳米颗粒诱导的 DNA 损伤中环 circ_009773 的功能和调控网络。

Identification of the function and regulatory network of circ_009773 in DNA damage induced by nanoparticles of neodymium oxide.

机构信息

School of Public Health, Baotou Medical College, Baotou 014030, Inner Mongolia, China.

School of Public Health, Guangzhou Medical University, Guangzhou 511436, Guangdong Province, China.

出版信息

Toxicol In Vitro. 2022 Feb;78:105271. doi: 10.1016/j.tiv.2021.105271. Epub 2021 Nov 3.

DOI:10.1016/j.tiv.2021.105271
PMID:34740776
Abstract

The health hazards of nanoparticles of neodymium oxide (NPs-NdO) have aroused public concern in recent years. Exposure to NPs-NdO can change the level of reactive oxygen species (ROS) that cause DNA damage and alter whole transcriptome expression profiles for micro (mi)RNA, circular (circ)RNA, long noncoding (lnc)RNA, and mRNA. However, there have been no reports to our knowledge about the role of circRNAs in DNA damage caused by NPs-NdO. In our study, we analyzed the circRNA expression profile of human bronchial epithelial cells(16HBE)exposed to 40 μg/ml NPs-NdO. Our results indicated that exposure produced 1025 up-regulated and 890 down-regulated circRNAs. Real-time quantitative polymerase chain reaction (qRT-PCR) was applied to verify some of the significantly changed circRNAs and demonstrated that circ_009773 was apparently down-regulated. Through exploration of its host gene function, we found that circ_009773 may be related to DNA damage. Functional experiments found that circ_009773 regulated NPs-NdO-induced DNA damage in 16HBE cells. A circ_009773-associated competing endogenous (ce)RNA network was constructed based on one differentially expressed (DE) circRNA, 74 DE miRNAs and 208 DE mRNAs. Module analysis identified hub genes related to DNA damage and repair and a protein-protein interaction (PPI) network was created.

摘要

近年来,氧化钕纳米粒子(NPs-NdO)的健康危害引起了公众的关注。暴露于 NPs-NdO 会改变活性氧(ROS)的水平,导致 DNA 损伤,并改变 micro (mi)RNA、环状 (circ)RNA、长链非编码 (lnc)RNA 和 mRNA 的全转录组表达谱。然而,据我们所知,还没有关于 circRNAs 在 NPs-NdO 引起的 DNA 损伤中的作用的报道。在我们的研究中,我们分析了暴露于 40μg/ml NPs-NdO 的人支气管上皮细胞(16HBE)中的 circRNA 表达谱。结果表明,暴露产生了 1025 个上调和 890 个下调的 circRNAs。实时定量聚合酶链反应(qRT-PCR)用于验证一些显著变化的 circRNAs,并表明 circ_009773 明显下调。通过探索其宿主基因功能,我们发现 circ_009773 可能与 DNA 损伤有关。功能实验发现 circ_009773 调节 16HBE 细胞中 NPs-NdO 诱导的 DNA 损伤。基于一个差异表达(DE)circRNA、74 个 DEmiRNA 和 208 个 DEmRNA,构建了 circ_009773 相关竞争性内源性(ce)RNA 网络。模块分析确定了与 DNA 损伤和修复相关的枢纽基因,并创建了蛋白质-蛋白质相互作用(PPI)网络。

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