EGR1 Down-regulation Mediated By Mir-377-3p Promotes BPDE-induced Malignant Transformation Of Human Lung Bronchial Epithelial Cells

Polycyclic aromatic hydrocarbons(PAHs),especially Benzo[a]pyrene(B[a]P),contained in cigarette smoke and air pollution,belong to a category of important carcinogens for lung cancer.The early molecular events and related mechanisms of B[a]P-induced cell transformation and tumor initiation remains unclear.In this study,we found that EGR1 was significantly down-regulated during mice lung carcinogenesis and human bronchial epithelial BEAS-2B cell transformation upon B[a]P and BPDE exposures,respectively.Overexpression of EGR1 inhibited the cell malignant transformation upon BPDE exposure.Furthermore,luciferase reporter assays showed that BPDE-induced miR-377-3p upregulation was crucial for inhibition of EGR1 by targeting its 3'UTR.Finally,the B[a]P exposure-induced molecular changes were examined by immunohistochemistry in clinical lung cancer tissues.Taken together,the results demonstrated that B[a]P 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.