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Nicotine downregulates microRNA‐200c to promote metastasis and the epithelial–mesenchymal transition in human colorectal cancer cells
Author(s) -
Lei Zhou,
Xiaomin Yang,
He Huang,
Jian Chen,
Xiaowu Xu
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26933
Subject(s) - epithelial–mesenchymal transition , colorectal cancer , microrna , metastasis , cancer research , mesenchymal stem cell , transition (genetics) , cancer , oncology , biology , medicine , microbiology and biotechnology , gene , genetics
Background Cigarette smoking is the most well‐established risk factor for colorectal cancer (CRC). However, the mechanisms of smoking‐associated colorectal carcinogenesis are poorly understood. Methods The effects of prediagnosis tobacco use on clinical characteristics, overall survival (OS), and recurrence‐free survival (RFS) were analyzed in 396 patients with CRC. Associations between smoking status and OS and RFS were evaluated using Cox’s proportional hazards regression. Furthermore, the effects of nicotine on the CRC cell lines SW620 and HT‐29 were evaluated using in vitro assays. Results “Ever smoking” was associated with elevated serum carcinoembryonic antigen, American Joint Committee on Cancer T category, metastasis, and poorer OS and RFS in patients with CRC (OS: hazard ratio [HR] = 1.74, 95% confidence interval [CI], 1.07–2.81, p = 0.025; RFS: HR = 1.66, 95% CI: 1.18–2.34, p = 0.004). MicroRNA (miR)‐200c was downregulated in CRC and tumor‐adjacent tissues from ever smokers compared with the corresponding tissues from never smokers with CRC. Nicotine inhibited miR‐200c expression in a dose‐ and time‐dependent manner in SW620 and HT‐29 CRC cell lines. Nicotine induced cell proliferation, migration, and invasion and promoted the epithelial–mesenchymal transition in SW620 and HT‐29 cells, and these effects were attenuated by overexpression of miR‐200c. Conclusion Our findings support the adverse effects of prediagnosis cigarette smoking on prognosis and clinical behavior in CRC. We demonstrate a novel oncogenic mechanism by which nicotine promotes growth and metastasis in CRC by downregulating miR‐200c.