J Cancer 2020; 11(19):5758-5767. doi:10.7150/jca.46976

Research Paper

PM2.5 downregulates MicroRNA-139-5p and induces EMT in Bronchiolar Epithelium Cells by targeting Notch1

Yunxia Wang1#, Yijue Zhong2#, Cheng Zhang1, Jiping Liao1✉, Guangfa Wang1✉

1. Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, China.
2. Department of Geriatrics, Jiangsu Provincial Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
#First authors with equal contributions to this manuscript.

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Wang Y, Zhong Y, Zhang C, Liao J, Wang G. PM2.5 downregulates MicroRNA-139-5p and induces EMT in Bronchiolar Epithelium Cells by targeting Notch1. J Cancer 2020; 11(19):5758-5767. doi:10.7150/jca.46976. Available from http://www.jcancer.org/v11p5758.htm

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PM2.5 was closely linked to lung cancer worldwide. However, the mechanism involved in PM2.5 induced lung cancer is still largely unknown. In this study, we performed chronic PM2.5 stimulation animal and cells model to investigate the carcinogenetic mechanisms of PM2.5 by targeting EMT through Notch1 signal pathway. Next, we focused on the miRNA involved in PM2.5 induced Notch1 pathway activation. We found chronic PM2.5 could induce EMT event in vivo and in vitro, while reducing miR-139-5p expression and activating Notch1 pathway meanwhile. And blocking Notch1 signal pathway by specific small molecule inhibitor could reverse PM2.5 induced EMT. Then, overexpression of miR-139-5p downregulated the expression of Notch1 protein in untreated 16HBE cells. Importantly, overexpression of miR-139-5p blocked Notch1 pathway activation and inhibited EMT event in PM2.5 treated cells. These results indicate that PM2.5 induces EMT event through Notch1 signal pathway and miR-139-5p is a novel regulator of PM2.5-induced EMT by targeting Notch1. Our conclusion is that overexpression of miR-139-5p can down-regulate the expression of Notch1 and reverse the occurrence of malignant lung events induced by chronic exposure to PM2.5.

Keywords: PM2.5, 16HBE, EMT, Notch1, miR-139-5p