GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Shanghai, China.
J Mol Med (Berl). 2012 Sep;90(9):1037-46. doi: 10.1007/s00109-012-0869-0. Epub 2012 Feb 11.
Abnormalities in signal transducer and activator of transcription (STAT) signaling, especially STAT3 and STAT5, are involved in the oncogenesis of several human cancers, including gastric cancer (GC). However, the downstream targets of STAT3 and STAT5 are not fully identified, and the precise roles and the prognostic value of STAT3 and STAT5 in GC have not been fully characterized. In this study, we used ChIP-on-chip to identify STAT3 and STAT5 target genes on a whole genome scale in AGS cells, a human GC cell line. A total of 2,514 and 1,314 genes were identified as STAT3 and STAT5 target genes, which were mainly related to cell growth, metabolism, differentiation, adhesion, immune response, and stress response. Furthermore, we depleted STAT3 and STAT5 with a small interfering RNA, respectively. Our results demonstrate that STAT3, but not STAT5, is involved in GC cell growth and cell cycle progression through regulation of gene expression, such as Bcl-2, p16(ink4a) and p21(waf1/cip1). Moreover, expression of pSTAT3(Tyr705) correlates with TNM stage, differentiation and survival, and is a significant prognostic factor in GC. Therefore, our findings provide novel evidence that STAT3 may be a potential therapeutic target for GC treatment and pSTAT3(Tyr705) expression can predict prognosis in GC.
信号转导子和转录激活子（STAT）信号的异常，特别是 STAT3 和 STAT5，参与了多种人类癌症的发生，包括胃癌（GC）。然而，STAT3 和 STAT5 的下游靶点尚未完全确定，STAT3 和 STAT5 在 GC 中的精确作用和预后价值尚未得到充分描述。在这项研究中，我们使用 ChIP-on-chip 在AGS 细胞（一种人 GC 细胞系）的全基因组范围内鉴定了 STAT3 和 STAT5 的靶基因。共鉴定出 2514 个和 1314 个基因分别作为 STAT3 和 STAT5 的靶基因，它们主要与细胞生长、代谢、分化、黏附、免疫反应和应激反应有关。此外，我们分别用小干扰 RNA 耗尽 STAT3 和 STAT5。我们的结果表明，STAT3 而不是 STAT5，通过调节基因表达，如 Bcl-2、p16(ink4a)和 p21(waf1/cip1)，参与 GC 细胞生长和细胞周期进程。此外，pSTAT3(Tyr705)的表达与 TNM 分期、分化和生存相关，是 GC 的一个重要预后因素。因此，我们的研究结果提供了新的证据，表明 STAT3 可能是 GC 治疗的潜在治疗靶点，pSTAT3(Tyr705)的表达可以预测 GC 的预后。
