Kang Wei, Tong Joanna H M, Chan Anthony W H, Zhao Junhong, Dong Yujuan, Wang Shiyan, Yang Weiqin, Sin Frankie M C, Ng Simon S M, Yu Jun, Cheng Alfred S L, To Ka Fai
Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, PR China.
J Transl Med. 2014 Mar 28;12:80. doi: 10.1186/1479-5876-12-80.
Yin 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.
In 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 and in vivo study 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.
YY1 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 proliferation in vitro and in 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.
Our 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.
阴阳1（YY1）是一种转录因子，可调节多种生物学过程，并且越来越被认为在肿瘤发生中起重要作用。YY1在胃腺癌（GAC）中的功能和临床意义尚未阐明。
在本研究中，通过MTT增殖试验、单层集落形成、细胞周期分析、信号通路分析、蛋白质印迹分析以及通过YY1敲低或过表达进行的体内研究，探讨了YY1在胃癌中的功能作用。使用YY1抗体对由247例临床GAC样本组成的组织芯片进行免疫组织化学研究。评估临床相关性和预后意义。
YY1表达在胃癌细胞系和原发性胃癌中上调。用siYY1敲低YY1可抑制细胞生长，诱导G1期积累和细胞凋亡。异位YY1表达增强体外和体内细胞增殖。在胃癌细胞中敲低YY1通过抑制Wnt/β-连环蛋白途径抑制增殖，而其过表达通过激活Wnt/β-连环蛋白途径发挥致癌特性。在原发性GAC样本中，YY1核表达与较短生存期相关，并预测早期GAC患者预后不良。
我们的数据表明YY1在胃癌发生中起作用。在早期GAC中，YY1可能是一个不良预后标志物，也可能是一个潜在的治疗靶点。
