Yin Yang 1 contributes to gastric carcinogenesis and its nuclear expression correlates with shorter survival in patients with early stage gastric adenocarcinoma.

Yin Yang 1 contributes to gastric carcinogenesis and its nuclear expression correlates with shorter survival in patients with early stage gastric adenocarcinoma.
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阴阳1促进胃癌发生,其核表达与早期胃腺癌患者的较短生存期相关

DOI:
10.1186/1479-5876-12-80
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发表时间:
2014-03-28
影响因子:
7.4
通讯作者:
To KF
To KF
中科院分区:
医学2区
文献类型:
--
作者:
Kang W;Tong JH;Chan AW;Zhao J;Dong Y;Wang S;Yang W;Sin FM;Ng SS;Yu J;Cheng AS;To KF

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阴阳1(Yin Yang 1,YY 1)是一种转录因子,调节多种生物学过程,在肿瘤的发生发展中起着重要作用。方法本研究采用MTT法、细胞周期分析、细胞单层集落形成实验、信号通路分析、Western blot分析、体内实验等方法,通过YY 1基因敲低或过表达,研究YY 1在胃癌中的功能作用。用YY 1抗体对247例临床GAC标本的组织芯片进行免疫组化研究。结果YY 1在胃癌细胞株和原发性胃癌中表达上调。siYY 1基因敲除YY 1后,细胞生长受到抑制,G1期细胞增多,细胞凋亡。YY 1的异位表达在体内外均能促进细胞增殖。YY 1基因敲除可抑制胃癌细胞Wnt/β-catenin通路,抑制细胞增殖,而其过表达可激活Wnt/β-catenin通路,发挥致癌作用。在原发性GAC样品中,YY 1核表达与较短的生存期和预测预后不良的早期GACs.ConclusionOur数据表明,YY 1有助于胃癌的发生。在早期的GACs中,YY 1可能作为一个预后不良的标志物,并可能作为一个潜在的治疗靶点。
BackgroundYin Yang 1 (YY1) is a transcription factor that regulates diverse biological processes and increasing recognized to have important roles in carcinogenesis. The function and clinical significance of YY1 in gastric adenocarcinoma (GAC) have not been elucidated.MethodsIn this study, the functional role of YY1 in gastric cancer was investigated by MTT proliferation assays, monolayer colony formation, cell cycle analysis, signaling pathway analysis, Western blot analysis andin vivostudy through YY1 knockdown or overexpression. Immunohistochemical study with YY1 antibody was performed on tissue microarray consisting of 247 clinical GAC samples. The clinical correlation and prognosis significance were evaluated.ResultsYY1 expression was up-regulated in gastric cancer cell lines and primary gastric cancers. Knocking down YY1 by siYY1 inhibited cell growth, inducing G1 phase accumulation and apoptosis. Ectopic YY1 expression enhanced cell proliferationin vitroandin vivo. Knocking down YY1 in gastric cancer cells suppressed proliferation by inhibiting Wnt/β-catenin pathway, whereas its overexpression exerted oncogenic property by activating Wnt/β-catenin pathway. In primary GAC samples, YY1 nuclear expression correlated with shorter survival and predicted poor prognosis in early stage GACs.ConclusionOur data demonstrated that YY1 contributes to gastric carcinogenesis in gastric cancer. In early stage GACs YY1 might serve as a poor prognostic marker and possibly as a potential therapeutic target.
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