Abstract
The hazards of particulate matter (PM2.5) on human respiratory health have been previously reported. However, the molecular mechanisms underlying PM2.5-induced lung carcinogenesis have rarely been studied. In the present study, we explored the effects of PM2.5 on the epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like properties in lung bronchial epithelial cells. We found that exposure of PM2.5 enhanced lung bronchial epithelial cell proliferation and EMT. In addition, the expression level of CSC-like biomarkers, CD133 and CD44, was significantly elevated by PM2.5 in vitro. Nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to participate in lung cancer. Loss of NEAT1 represses the malignant transformation of BEAS-2B and HBE cells induced by PM2.5. NEAT1 interacts with microRNA (miR)-582-5p, and miR-582-5p reverses the pro-tumor effects of NEAT1 overexpression. Hypoxia-inducible factor (HIF)-1α is an important transcription factor in the pathological responses to hypoxia. HIF-1α was a predicted target for miR-582-5p, and a direct correlation between them was identified. Inhibitors of miR-582-5p rescued HIF-1α expression, which was attenuated by a lack of NEAT1. In conclusion, PM2.5 increased NEAT1 expression, which, by binding with miR-582-5p, released HIF-1α and promoted EMT and the acquisition of CSC-like characteristics.
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The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
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This work was supported by grants from The National Key Research and Development Program of China (grant no. 2018YFC1313600).
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P.J. and S.H. conceived and designed the study; P.J. and L.X. performed the experiments; Z.L., G.X., L.X., W.H., Q.W., and P.J. analyzed the data; P.J. and S.H. interpreted the data of the experiments; P.J. prepared the figures; P.J. and S.L. drafted the manuscript; Z.L., L.X., G.X., W.H., Q.W., and P.J. edited and revised manuscript; S.L. approved the final version of manuscript.
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Jiang, P., Hao, S., Xie, L. et al. LncRNA NEAT1 contributes to the acquisition of a tumor like-phenotype induced by PM 2.5 in lung bronchial epithelial cells via HIF-1α activation. Environ Sci Pollut Res 28, 43382–43393 (2021). https://doi.org/10.1007/s11356-021-13735-7
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DOI: https://doi.org/10.1007/s11356-021-13735-7