Increasing evidence shows that circular RNA (circRNA) plays an important role in the progression of lung cancer. In this study, we found that has_circ_0000043 was highly expressed in 16HBE-T human bronchial epithelial cells that were malignantly transformed by benzo[a]pyrene-trans-7,8-diol-9,10-epoxide via circRNA microarray. We verified that hsa_circ_0000043 was also significantly overexpressed in lung cancer cell lines and tissues. Moreover, hsa_circ_0000043 overexpression was positively correlated with poor clinicopathological parameters, such as tumor-node metastasis stage, distant metastasis, lymph-node metastasis, and overall survival. In vitro assays revealed that hsa_circ_0000043 inhibition suppressed 16HBE-T cell proliferation, migration, and invasion. Furthermore, hsa_circ_0000043 inhibition suppressed tumor growth in a mouse xenograft model. We discovered that hsa_circ_0000043 binds with miR-4492, acting as a miR-4492 sponge. Decreased miR-4492 expression was also associated with poor clinicopathological parameters. Thus, hsa_circ_0000043 was shown to contribute to the proliferation, malignant transformation ability, migration, and invasion of 16HBE-T cells via miR-4492 sponging and BDNF and STAT3 involvement.

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http://dx.doi.org/10.1093/toxsci/kfad060DOI Listing

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