Fu You, Li Bin, Yun Jun, Xu Jie, Meng Qingtao, Li Xiaobo, Chen Rui
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, PR China.
School of Public Health, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, PR China.
Ecotoxicol Environ Saf. 2021 Jul 1;217:112242. doi: 10.1016/j.ecoenv.2021.112242. Epub 2021 Apr 22.
Exposure to fine particulate matter (PM) in outdoor air is carcinogenic and associated with the development of lung cancer; however, the underlying mechanism remains unclear. In the present study, the profiles of lncRNA, microRNA and mRNA expression profiles in human bronchial epithelia (HBE) following exposure to PM, diesel exhaust particles (DEPs), or aluminum oxide nanoparticles (AlO NPs) were explored by microarray to reveal the lncRNA-microRNA-mRNA network participating in the malignant transformation of HBE cells following long-term PM exposure. The results showed that lncRNA SOX2 overlapping transcript (SOX2-OT) was significantly induced in HBE cells exposed to PM, DEPs, or AlO NPs, acting as a sponge to microRNA-345-5p, which subsequently increased the expression levels of epidermal growth factor receptor (EGFR). EGFR is a therapeutic target in non-small cell lung cancer. Here, we found that SOX2-OT is an upstream trigger of EGFR in HBE cells during long-term PM exposure. Importantly, SOX2-OT knockdown effectively reduced the colony formation and migration capacities of HBE cells, compared to the wild type control. Collectively, SOX2-OT/microRNA-345-5p/EGFR is a ceRNA mechanism underlying the malignant transformation of bronchial epithelia exposed to PM, which improves our understanding of the association between ambient PM exposure and the development of lung cancer.
暴露于室外空气中的细颗粒物（PM）具有致癌性，并与肺癌的发生有关；然而，其潜在机制仍不清楚。在本研究中，通过微阵列探索了人支气管上皮细胞（HBE）在暴露于PM、柴油废气颗粒（DEP）或氧化铝纳米颗粒（AlO NP）后lncRNA、microRNA和mRNA的表达谱，以揭示长期暴露于PM后参与HBE细胞恶性转化的lncRNA- microRNA- mRNA网络。结果显示，在暴露于PM、DEP或AlO NP的HBE细胞中，lncRNA SOX2重叠转录本（SOX2-OT）显著上调，它作为microRNA-345-5p的海绵，随后增加了表皮生长因子受体（EGFR）的表达水平。EGFR是非小细胞肺癌的治疗靶点。在此，我们发现SOX2-OT是长期暴露于PM期间HBE细胞中EGFR的上游触发因子。重要的是，与野生型对照相比，敲低SOX2-OT可有效降低HBE细胞的集落形成和迁移能力。总的来说，SOX2-OT/microRNA-345-5p/EGFR是PM暴露导致支气管上皮恶性转化的一种ceRNA机制，这增进了我们对环境PM暴露与肺癌发生之间关联的理解。
