Peroxiredoxin 1 promotes invasion and migration by regulating epithelial-to-mesenchymal transition during oral carcinogenesis.

Peroxiredoxin 1 promotes invasion and migration by regulating epithelial-to-mesenchymal transition during oral carcinogenesis.
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过氧化还原蛋白 1 通过调节口腔癌发生过程中的上皮间质转化来促进侵袭和迁移

DOI:
10.18632/oncotarget.9705
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发表时间:
2016-07-26
期刊:
影响因子:
--
通讯作者:
Tang X
Tang X
中科院分区:
其他
文献类型:
--
作者:
Niu W;Zhang M;Chen H;Wang C;Shi N;Jing X;Ge L;Chen T;Tang X

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吸烟是口腔鳞状细胞癌(OSCC)的主要危险因素。此前,我们发现尼古丁上调 OSCC 细胞中重要的抗氧化酶过氧化还原酶 1 (Prx1) 和核因子 kappa B (NFκB)。然而,Prx1在口腔癌发生中的分子机制仍不清楚。为了加深对 Prx1 在烟草相关口腔癌发生级联过程中功能作用的理解,我们在 30 个原发性口腔肿瘤(15 个来自患有 OSCC 的吸烟者和 15 个来自患有 OSCC 的非吸烟者)和 10 个正常口腔粘膜标本中对 Prx1、NFκB 和上皮间质转化 (EMT) 标记物(包括 E-钙粘蛋白、波形蛋白和 Snail)进行了表征 来自健康个体。吸烟者 OSCC 肿瘤中 Prx1、核 NFκB、vimentin 和 Snail 的表达水平高于非吸烟 OSCC 患者或健康对照者。 E-cadherin的表达水平呈现相反的趋势。 Prx1 沉默可抑制尼古丁诱导的 SCC15 细胞体外 EMT、细胞侵袭和迁移。此外,Prx1 激活 SCC15 细胞中的 NFκB 通路。因此,Prx1 可能在烟草相关的 OSCC 中发挥致癌作用,从而作为化学预防和治疗干预的靶点。
Tobacco smoking is the major risk factor for oral squamous cell carcinoma (OSCC). Previously, we found that nicotine up-regulates peroxiredoxin 1 (Prx1), an important antioxidant enzyme, and nuclear factor kappa B (NFκB) in OSCC cells. However, the molecular mechanism of Prx1 in oral carcinogenesis remains obscure. To improve our understanding of the functional role of Prx1 during the cascade of tobacco-associated oral carcinogenesis, we characterized Prx1, NFκB, and epithelial-to-mesenchymal transition (EMT) markers including E-cadherin, vimentin and Snail in 30 primary oral tumors (15 from smokers with OSCC and 15 from non-smokers with OSCC) and 10 normal oral mucosa specimens from healthy individuals. The expression levels of Prx1, nuclear NFκB, vimentin and Snail were higher in the tumors from smokers with OSCC than in those from non-smokers with OSCC or the healthy controls. The expression levels of E-cadherin showed an opposite trend. Prx1 silencing suppressed the nicotine-induced EMT, cell invasion and migration in SCC15 cells in vitro. Furthermore, Prx1 activated the NFκB pathway in SCC15 cells. Prx1 might therefore play an oncogenic role in tobacco-related OSCC and thus serve as a target for chemopreventive and therapeutic interventions.
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