Acquisition cancer stemness, mesenchymal transdifferentiation, and chemoresistance properties by chronic exposure of oral epithelial cells to arecoline

doi:10.18632/oncotarget.11432

中山醫學大學機構典藏 CSMUIR > 口腔醫學院 > 牙醫學系暨碩士班 > 博碩士論文 > Item 310902500/19229

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/19229

Title:	Acquisition cancer stemness, mesenchymal transdifferentiation, and chemoresistance properties by chronic exposure of oral epithelial cells to arecoline
Authors:	TY, Wang CY, Peng SS, Lee MY, Chou CC, Yu YC, Chang
Contributors:	中山醫學大學
Keywords:	arecoline;cancer stemness;oral squamous cell carcinomas
Date:	2016-12
Issue Date:	2018-06-20T09:01:18Z (UTC)
Publisher:	Oncotarget
ISSN:	1949-2553
Abstract:	Oral squamous cell carcinoma (OSCC), one of the most deadliest malignancies in the world, is caused primarily by areca nut chewing in Southeast Asia. The mechanisms by which areca nut participates in OSCC tumorigenesis are not well understood. In this study, we investigated the effects of low dose long-term arecoline (10 μg/mL, 90-days), a major areca nut alkaloid, on enhancement cancer stemness of human oral epithelial (OE) cells. OE cells with chronic arecoline exposure resulted in increased ALDH1 population, CD44 positivity, stemness-related transcription factors (Oct4, Nanog, and Sox2), epithelial-mesenchymal transdifferentiation (EMT) traits, chemoresistance, migration/invasiveness/anchorage independent growth and in vivo tumor growth as compared to their untreated controls. Mechanistically, ectopic miR-145 over-expression in chronic arecoline-exposed OE (AOE) cells inhibited the cancer stemness and xenografic. In AOE cells, luciferase reporter assays further revealed that miR-145 directly targets the 3' UTR regions of Oct4 and Sox2 and overexpression of Sox2/Oct4 effectively reversed miR-145-regulated cancer stemness-associated phenomenas. Additionally, clinical results further revealed that Sox2 and Oct4 expression was inversely correlated with miR-145 in the tissues of areca quid chewing-associated OSCC patients. This study hence attempts to provide novel insight into areca nut-induced oral carcinogenesis and new intervention for the treatment of OSCC patients, especially in areca nut users.
URI:	http://dx.doi.org/10.18632/oncotarget.11432 https://ir.csmu.edu.tw:8080/ir/handle/310902500/19229
Relation:	Oncotarget. 2016; 7:84072-84081
Appears in Collections:	[牙醫學系暨碩士班] 博碩士論文

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