AUTHOR=Ke Xinxin , He Lulu , Wang Runan , Shen Jing , Wang Zhengyang , Shen Yifei , Fan Longjiang , Shao Jimin , Qi Hongyan 

TITLE=miR-377-3p-Mediated EGR1 Downregulation Promotes B[a]P-Induced Lung Tumorigenesis by Wnt/Beta-Catenin Transduction

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.699004

DOI=10.3389/fonc.2021.699004

ISSN=2234-943X

ABSTRACT=Polycyclic aromatic hydrocarbons (PAHs), particularly Benzo[a]pyrene (B[a]P), contained in cigarette smoke and air pollution, belong to a category of important carcinogens for lung cancer. However, early molecular events and related regulatory effects of B[a]P-mediated cell transformation and tumor initiation remain unclear. Here we showed that EGR1 was significantly down-regulated during human bronchial epithelial cell transformation and mice lung carcinogenesis upon B[a]P and its active form BPDE exposure, respectively. In contrast, overexpression of EGR1 inhibited the BPDE-induced cell malignant transformation. Moreover, miR-377-3p was strongly enhanced by BPDE/B[a]P. It was crucial for the inhibition of EGR1 expression by targeting EGR1’s 3'UTR. MiR-377-3p antagomir reversed the effect of EGR1 downregulation in the cell malignant transformation and tumour initiation models. The B[a]P-induced molecular changes were evaluated by immunohistochemistry in clinical lung cancer tissues and examined with clinic database. Furthermore, EGR1 inhibition was also involved in the regulation of Wnt/-catenin transduction, which could promote the lung tumorigenesis following B[a]P/BPDE exposure. Taken together, the results demonstrated that Benzo[a]pyrene exposure may induce lung tumorigenesis through miR-377-3p mediated reduction of EGR1 expression, suggesting an important role of EGR1 in PAH-induced lung carcinogenesis.