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EDD1通过miR-22预测胃癌预后并在体内外调节胃癌生长。

EDD1 predicts prognosis and regulates gastric cancer growth in vitro and in vivo via miR-22.

作者信息

Yang Min, Jiang Nan, Cao Qi-Wei, Sun Qing

出版信息

Biol Chem. 2016 Apr 28. doi: 10.1515/hsz-2015-0279.

Abstract

Gastric cancer is the most common digestive malignant tumor worldwild. EDD1 was reported to be frequently amplified in several tumors and played an important role in the tumorigenesis process. However, the biological role and potential mechanism of EDD1 in gastric cancer remains poorly understood. In this study, we are aim to investigate the effect of EDD1 on gastric cancer progression and to explore the underlying mechanism. The results showed the significant up-regulation of EDD1 in -gastric cancer cell tissues and lines. The expression level of EDD1 was also positively associated with advanced clinical stages and predicted poor overall patient survival and poor disease-free patient survival. Besides, EDD1 knockdown markedly inhibited cell viability, colony formation, and suppressed tumor growth. Opposite results were obtained in gastric cancer cells with EDD1 overexpression. EDD1 knockdown was also found to induce gastric cancer cells apoptosis. Further investigation indicated that the oncogenic role of EDD1 in regulating gastric cancer cells growth and apoptosis was related to its PABC domain and directly through targeting miR-22, which was significantly down-regulated in gastric cancer tissues. Totally, our study suggests that EDD1 plays an oncogenic role in gastric cancer and may be a potential therapeutic target for gastric cancer.

摘要

胃癌是全球最常见的消化系统恶性肿瘤。据报道,EDD1在多种肿瘤中经常扩增,并在肿瘤发生过程中发挥重要作用。然而,EDD1在胃癌中的生物学作用和潜在机制仍知之甚少。在本研究中,我们旨在研究EDD1对胃癌进展的影响,并探讨其潜在机制。结果显示,EDD1在胃癌细胞组织和细胞系中显著上调。EDD1的表达水平也与晚期临床分期呈正相关,并预示患者总体生存率和无病生存率较差。此外,敲低EDD1可显著抑制细胞活力、集落形成,并抑制肿瘤生长。在过表达EDD1的胃癌细胞中得到了相反的结果。还发现敲低EDD1可诱导胃癌细胞凋亡。进一步研究表明,EDD1在调节胃癌细胞生长和凋亡中的致癌作用与其PABC结构域有关,并且直接靶向miR-22,miR-22在胃癌组织中显著下调。总的来说,我们的研究表明EDD1在胃癌中发挥致癌作用,可能是胃癌的一个潜在治疗靶点。

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