Biomaterial Database

Nicotine downregulates microRNA-200c to promote metastasis and the epithelial-mesenchymal transition in human colorectal cancer cells. 2019

Zhou Lei, and Yang Xiaomin, and Huang He, and Chen Jian, and Xu Xiaowu

Department of Gastrointestinal Surgery, the 2nd Affiliated Hospital and Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Cigarette smoking is the most well-established risk factor for colorectal cancer (CRC). However, the mechanisms of smoking-associated colorectal carcinogenesis are poorly understood. 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. "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. 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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009361	Neoplasm Invasiveness	Ability of neoplasms to infiltrate and actively destroy surrounding tissue.	Invasiveness, Neoplasm,Neoplasm Invasion,Invasion, Neoplasm
D009538	Nicotine	Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.	Nicotine Bitartrate,Nicotine Tartrate
D002465	Cell Movement	The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.	Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000073865	Cigarette Smoking	The SMOKING of CIGARETTES.	Smoking, Cigarette
D012189	Retrospective Studies	Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.	Retrospective Study,Studies, Retrospective,Study, Retrospective