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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预后不良相关。

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

机构信息

Department of Gastroenterology, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.

出版信息

Biochem Biophys Res Commun. 2013 Jul 26;437(2):192-8. doi: 10.1016/j.bbrc.2013.05.123. Epub 2013 Jun 6.

DOI:10.1016/j.bbrc.2013.05.123
PMID:23747727
Abstract

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 LSD1 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.

摘要

最近的研究阐明了赖氨酸特异性脱甲基酶 1(LSD1)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,LSD1 是组蛋白去甲基酶的成员之一。然而,LSD1 在食管鳞状细胞癌(ESCC)患者中的表达尚不清楚。在这里,我们报道 LSD1 在癌组织中的表达升高,并与 ESCC 患者的淋巴结转移和总体生存率较差相关。与 EC109 细胞相比,侵袭性癌细胞系 KYSE450 和 KYSE150 中 LSD1 的表达上调。使用 LSD1 特异性 shRNA 的慢病毒递送敲低 LSD1 可阻断 ESCC 细胞的体外迁移和侵袭。此外,LSD1 抑制剂曲利苯蓝以剂量依赖的方式抑制 H3K4me2 去甲基化并减弱细胞迁移和侵袭性。综上所述,这些数据表明 LSD1 是一种潜在的预后标志物,可能是抑制 ESCC 侵袭和转移的分子靶点。

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