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

Wei Kang,Shiyan Wang,Frankie Mc Sin,Alfred Sl Cheng,Anthony Wh Chan,Jun Yu,Weiqin Yang,Ka Fai To,Yujuan Dong,Joanna Hm Tong,Junhong Zhao,Simon Sm Ng

doi:10.1186/1479-5876-12-80

Abstract

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 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.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 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.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.

Highlights

Yin Yang 1 (YY1) is a transcription factor that regulates diverse biological processes and increasing recognized to have important roles in carcinogenesis
Up-regulation of YY1 in gastric cancer cell lines and primary gastric adenocarcinoma (GAC) samples Up-regulation of YY1 protein was detected in 9 gastric cancer cell lines by Western blot analysis (Figure 1A)
YY1 reportedly activates the expression of human epidermal growth factor receptor 2 (ERBB2) [8,9], which is overexpressed in approximately 30% of breast cancers and correlates with poor prognosis

Summary

Introduction

Yin Yang 1 (YY1) is a transcription factor that regulates diverse biological processes and increasing recognized to have important roles in carcinogenesis. GAC is one of the leading causes of cancerrelated death worldwide, accounting for approximately 740,000 cases of cancer-related death annually [2]. While various factors such as H. pylori infection, genetic, Yin Yang 1 (YY1) is a ubiquitously distributed transcription factor belonging to the Gli-Kruepple class of Zinc-finger proteins [4]. YY1 has diverse and complex biological functions and is involved in both repression and activation of numerous genes that play essential roles in a multitude of biological processes [5]. YY1 has been found to negatively regulate several tumor suppressor genes such as p27 [10], p16 [11], p73 [12] and p53 [13]

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