A novel lncRNA, loc107985872, promotes lung adenocarcinoma progression via the notch1 signaling pathway with exposure to traffic-originated PM2.5 organic extract

A novel lncRNA, loc107985872, promotes lung adenocarcinoma progression via the notch1 signaling pathway with exposure to traffic-originated PM2.5 organic extract
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一种新型 lncRNA,loc107985872,通过暴露于交通来源的 PM2.5 有机提取物,通过 notch1 信号通路促进肺腺癌进展

DOI:
10.1016/j.envpol.2020.115307
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发表时间:
2020-11-01
影响因子:
8.9
通讯作者:
Wang, Yan
Wang, Yan
中科院分区:
环境科学与生态学2区
文献类型:
--
作者:
Guo, Huaqi;Feng, Yan;Wang, Yan

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PM2.5 污染是中国一个重要而紧迫的问题,会增加死亡率和住院率。交通产生的PM2.5有机成分(tPo)主要含有多环芳烃(PAHs)。研究表明,PAHs可以促进肺腺癌细胞的侵袭、转移和癌症干细胞特性,但确切的毒理学机制尚不清楚。在本研究中,我们研究了lncRNA对tPo诱导的肺腺癌进展的影响以及lncRNA-信号通路相互作用介导的潜在机制。我们发现,长期tPo治疗上调了loc107985872的表达,从而通过notch1通路进一步促进肺腺癌细胞中的细胞侵袭和迁移、EMT和癌症干细胞特性。同时,通过loc107985872激活notch1信号通路可能与其上游蛋白(如ADAM17、PSEN1和DLL1)的异常高表达有关。此外,tPo 暴露可诱导 EMT 并通过体内 notch1 信号通路获得癌症干细胞样特性。总之,tPo上调的loc107985872通过notch1信号通路促进肺腺癌进展。 (C) 2020 Elsevier Ltd. 保留所有权利。
PM2.5 pollution is an important and urgent problem in China that can increase mortality and hospital admissions. Traffic-originated PM2.5 organic component (tPo) mainly contains polycyclic aromatic hydrocarbons (PAHs). Research has shown that PAHs can promote invasion, metastasis, and cancer stem cell properties in lung adenocarcinoma cells, but the exact toxicological mechanism is unknown. In the present study, we investigated the effect of lncRNAs on the progression of lung adenocarcinoma induced by tPo and the underlying mechanisms mediated by lncRNA-signaling pathway interactions. We found that chronic tPo treatment upregulated the expression of loc107985872, which further promoted cell invasion and migration, EMT and cancer stem cell properties via notch1 pathway in lung adenocarcinoma cells. Meanwhile, activation of the notch1 signaling pathway through loc107985872 might be associated with abnormally high expression of its upstream proteins, such as ADAM17, PSEN1 and DLL1. Moreover, tPo exposure induced EMT and the acquisition of cancer stem cell-like properties via the notch1 signaling pathway in vivo. In summary, loc107985872 upregulated by tPo promoted lung adenocarcinoma progression via the notchl signaling pathway. (C) 2020 Elsevier Ltd. All rights reserved.