CircRNA-mediated ceRNA network: micron-sized quartz silica particles induce apoptosis in primary human airway epithelial cells.

IF 2.7 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics
Jiazi Ma, Bing Han, Yong Yang, Yu Zhang, Mao Cao, Wenyue Cao, Wei Zhang, Mengjie Cheng, Guanqun Cui, Zhongjun Du, Shangya Chen
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引用次数: 0

Abstract

This paper studies the toxic effect of micron-sized quartz silica particles on primary human airway epithelial cells (AECs) and the molecular mechanism of its induction of apoptosis. Studies have found that micron-sized quartz silica particles cause AECs damage by activating cell apoptosis. By constructing a competitive endogenous RNA (ceRNA) network, it was identified that three circRNAs (hsa_circ_0052203, hsa_circ_0022429, hsa_circ_0052264) and four key miRNAs (hsa-miR-4646-5p, hsa-miR-150-3p, hsa-miR-6798-3p, hsa-miR-6756-5p) play key roles in regulating apoptosis. In addition, seven mRNAs (LMNB1, TP53AIP1, CASP10, BCL2, LMNB2, CFLAR and ITPR1) were significantly associated with the apoptosis. Functional enrichment analysis indicated that these genes were involved in biological processes such as nuclear lysis, hypoxia response and DNA damage. This study has for the first time revealed the role of the ceRNA network in the apoptosis of AECs induced by micron-sized quartz silica particles, providing new molecular targets and therapeutic ideas for the early pathogenesis of silicosis.

circrna介导的ceRNA网络:微米级石英颗粒诱导人气道上皮细胞凋亡
本文研究微米级石英二氧化硅颗粒对人气道上皮细胞(AECs)的毒性作用及其诱导细胞凋亡的分子机制。研究发现,微米级的石英二氧化硅颗粒通过激活细胞凋亡导致aec损伤。通过构建竞争性内源性RNA (ceRNA)网络,发现3个circRNAs (hsa_circ_0052203、hsa_circ_0022429、hsa_circ_0052264)和4个关键miRNAs (hsa-miR-4646-5p、hsa-miR-150-3p、hsa-miR-6798-3p、hsa-miR-6756-5p)在调控细胞凋亡中发挥关键作用。此外,7种mrna (LMNB1、TP53AIP1、CASP10、BCL2、LMNB2、CFLAR和ITPR1)与细胞凋亡显著相关。功能富集分析表明,这些基因参与了核裂解、缺氧反应和DNA损伤等生物过程。本研究首次揭示了ceRNA网络在微米级石英二氧化硅颗粒诱导AECs凋亡中的作用,为矽肺早期发病机制提供了新的分子靶点和治疗思路。
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来源期刊
CiteScore
6.60
自引率
3.10%
发文量
66
审稿时长
6-12 weeks
期刊介绍: Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment.
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