Department of Gastroenterology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, PR China.
Mol Med Rep. 2011 Nov-Dec;4(6):1075-82. doi: 10.3892/mmr.2011.543. Epub 2011 Jul 28.
Gastric carcinoma is among the most prevalent malignancies, and a leading cause of cancer deaths worldwide. The Hippo pathway defines a novel signaling pathway regulating cell proliferation. The key factor in this kinase cascade is the transcriptional co-activator yes-associated protein (YAP), which is constitutively activated in various types of cancer, including gastric carcinoma. To determine the effect on SGC7901 gastric cancer cells after inhibition of the YAP expression, we used lentivirus-derived small hairpin RNA (shRNA) against YAP. The YAP-specific shRNA significantly suppressed YAP expression at the mRNA and protein levels, reduced cancer cell proliferation and promoted cancer cell apoptosis. It was also found that YAP knockdown significantly increased the G0/G1 cell population and reduced expression levels of a number of genes crucial to cell proliferation and apoptosis, including Ki-67, proliferating cell nuclear antigen (PCNA), survivin and cyclin D1. Thus, our data suggested that knockdown of YAP expression plays a significant role in gastric cancer cell proliferation and apoptosis. Therefore, the YAP gene serves as a potential therapeutic target in gastric cancers.
胃癌是最常见的恶性肿瘤之一，也是全球癌症死亡的主要原因。Hippo 通路定义了一种新的信号通路，调节细胞增殖。这个激酶级联反应的关键因素是转录共激活因子 yes 相关蛋白 (YAP)，它在包括胃癌在内的各种类型的癌症中被持续激活。为了确定抑制 YAP 表达后对 SGC7901 胃癌细胞的影响，我们使用了针对 YAP 的慢病毒衍生短发夹 RNA (shRNA)。YAP 特异性 shRNA 显著抑制 YAP 在 mRNA 和蛋白质水平的表达，减少癌细胞增殖并促进癌细胞凋亡。还发现 YAP 敲低显著增加了 G0/G1 细胞群体，并降低了许多对细胞增殖和凋亡至关重要的基因的表达水平，包括 Ki-67、增殖细胞核抗原 (PCNA)、存活素和细胞周期蛋白 D1。因此，我们的数据表明，YAP 表达的敲低在胃癌细胞增殖和凋亡中起重要作用。因此，YAP 基因是胃癌的潜在治疗靶点。
