High expression of lysine-specific demethylase 1 correlates with poor prognosis of patients with esophageal squamous cell carcinoma

High expression of lysine-specific demethylase 1 correlates with poor prognosis of patients with esophageal squamous cell carcinoma
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赖氨酸特异性去甲基化酶1的高表达与食管鳞状细胞癌患者的不良预后相关

DOI:
10.1016/j.bbrc.2013.05.123
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发表时间:
2013-07-26
影响因子:
3.1
通讯作者:
Chen, Dongfeng
Chen, Dongfeng
中科院分区:
生物学4区
文献类型:
--
作者:
Yu, Yanyan;Wang, Bin;Chen, Dongfeng

文献摘要

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赖氨酸特异性去甲基化酶1(LSD 1)是组蛋白去甲基化酶的一个成员,近年来的研究阐明了LSD 1在肿瘤抑制/促进基因和肿瘤生长的表观遗传调控中的作用。然而,LSD 1在食管鳞状细胞癌(ESCC)患者中的表达仍然未知。在这里,我们报告了LSDI在癌组织中的表达升高,并与ESCC患者的淋巴结转移和较差的总生存期相关。与EC 109细胞相比,侵袭性癌细胞系KYSE 450和KYSE 150中LSD 1的表达不受调节。使用LSD 1特异性shRNA的慢病毒递送敲除LSD 1,在体外废除了ESCC细胞的迁移和侵袭。此外,LSD 1抑制剂反苯环丙胺以剂量依赖性方式抑制H3 K4 me 2去甲基化并减弱细胞运动性和侵袭性。综上所述,这些数据表明,LSD 1是一个潜在的预后指标,并可能是一个分子靶点,抑制浸润和转移的食管鳞癌。(C)2013作者爱思唯尔公司出版All rights reserved.
Recent studies have elucidated the role of lysine-specific demethylase 1 (LSD1), a member of the histone demethylases, in epigenetic regulation of tumor suppressing/promoting genes and neoplastic growth. However, the expression of LSD1 in patients with esophageal squamous cell carcinoma (ESCC) is still unknown. Here, we reported that LSDI expression was elevated in cancerous tissue and correlated with lymph node metastasis and poorer overall survival in patients with ESCC. Compared to EC109 cells, LSD1 expression was unregulated in aggressive cancer cell lines KYSE450 and KYSE150. Knockdown of LSD1 using lentivirus delivery of LSD1-specific shRNA abrogated the migration and invasion of ESCC cells in vitro. Further, a LSD1 inhibitor, tranylcypromine, suppressed H3K4me2 demethylation and attenuated cellular motility and invasiveness in a dose-dependent manner. Taken together, these data suggested that LSD1 was a potential prognostic maker and may be a molecular target for inhibiting invasion and metastasis in ESCC. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.