Aryl hydrocarbon receptor activated by benzo (a) pyrene promotes SMARCA6 expression in NSCLC

Release time:2020-07-13

Impact Factor:5.177

Journal:Am J Cancer Res

Key Words:AhR; BaP; SMARCA6; lung cancer; smoking

Abstract:Recent studies suggest that individual subunits of chromatin-remodeling complexes generate epigenetically specific signaling in tumorigenicity. The impact of environmental factors on the chromatin-remodeling factor has not been thoroughly elucidated to date. We detected the expression level of SMARCA6 (SWI/SNF2-Related, Matrix-Associated, Actin-Dependent Regulator of Chromatin, Subfamily A, Member 6) in NSCLC (Non-small-cell lung carcinoma) and measured it through quantitative real-time PCR (qRT-PCR) and immunohistochemistry. The effects of BaP on proliferation and cell cycle progression were evaluated using MTT, colony formation and FACS analyses. Tumor growth in vivo was observed in a xenograft model. ChIP and qPCR were performed to validate that SMARCA6 was a potential target of AhR in NSCLC. As a result, BaP increased SMARCA6 expression. Smoking was linked with elevated SMARCA6 expression in NSCLC. BaP promoted cancer progression in vitro and in vivo. ChIP assay confirmed that BaP increases SMARCA6 expression via recruitment of AhR and induces SMARCA6 expression by facilitating AhR translocation to the nucleus. Furthermore, inhibition of AhR expression decreases SMARCA6 expression in NSCLC. Finally, knockdown of SMARCA6 attenuates BaP-induced cancer progression. This study demonstrates that BaP promotes proliferation by activation of AhR, which promotes SMARCA6 expression, and may identify new diagnostic and therapeutic targets in lung cancer.

Co-author:Min Wang, Banglun Qian, Lianlian Ouyang, Ying Shi, Na Liu, Ling Chen, Desheng Xiao, Xiang Wang, Ya Cao, Wenliang Liu

First Author:Chao Mao

Correspondence Author:Shuang Liu, Yongguang Tao

Volume:8(7)

Page Number:1214-1227

Translation or Not:no

Date of Publication:2018-07-01

Included Journals:SCI