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EZH2 通过抑制 p21 的表达促进胃癌细胞的增殖。

EZH2 promotes gastric cancer cells proliferation by repressing p21 expression.

机构信息

Department of General Surgery, Huzhou Central Hospital, Huzhou, People's Republic of China.

Department of Obstetrics and Gynecology, Huzhou Central Hospital, Huzhou, 313000, People's Republic of China.

出版信息

Pathol Res Pract. 2019 Jun;215(6):152374. doi: 10.1016/j.prp.2019.03.003. Epub 2019 Mar 4.

DOI:10.1016/j.prp.2019.03.003
PMID:30952377
Abstract

EZH2 is a core component of the polycomb repressive complex 2 (PRC2), which catalyzes trimethylation of histone H3 lysine 27 (H3K27me3) and promotes carcinogenesis by epigenetically silencing many tumor suppressor genes. Increased EZH2 expression is a marker of advanced and metastatic in many cancers, including lung, prostate and breast cancer, and it has been considered as a potential novel therapeutic target. However, the clinical significance and molecular mechanisms of EZH2 controlling gastric cancer cell proliferation and invasion are not well documented. In this study, immunohistochemical analysis was conducted to investigate the EZH2 expression in gastric cancer. We found that EZH2 levels were increased in gastric cancer tissues compared with adjacent normal tissues. Moreover, patients with high levels of EZH2 expression had a relatively poor prognosis. Furthermore, knockdown of EZH2 expression by siRNA could impair cell proliferation and invasion both in vitro and vivo. Finally, we found that EZH2 influences gastric cancer cells proliferation partly through regulating p21 expression. Our findings present that EZH2 over-expression can be identified as a poor prognostic biomarker in gastric cancer.

摘要

EZH2 是多梳抑制复合物 2(PRC2)的核心组成部分,它催化组蛋白 H3 赖氨酸 27(H3K27me3)的三甲基化,并通过表观遗传沉默许多肿瘤抑制基因促进致癌作用。在包括肺癌、前列腺癌和乳腺癌在内的许多癌症中,EZH2 表达增加是晚期和转移的标志物,它已被认为是一种潜在的新型治疗靶点。然而,EZH2 控制胃癌细胞增殖和侵袭的临床意义和分子机制尚未得到充分证明。在这项研究中,进行了免疫组织化学分析以研究胃癌中的 EZH2 表达。我们发现,与相邻正常组织相比,EZH2 水平在胃癌组织中升高。此外,EZH2 高表达的患者预后相对较差。此外,通过 siRNA 敲低 EZH2 表达可损害体外和体内的细胞增殖和侵袭。最后,我们发现 EZH2 通过调节 p21 表达影响胃癌细胞的增殖。我们的研究结果表明,EZH2 过表达可作为胃癌的不良预后生物标志物。

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