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靶向YAP基因的小干扰RNA抑制严重联合免疫缺陷小鼠胃癌的生长及肿瘤转移。

siRNA targeting YAP gene inhibits gastric carcinoma growth and tumor metastasis in SCID mice.

作者信息

Zhou Zhou, Zhu Jin-Shui, Gao Cai-Ping, Li Liang-Ping, Zhou Chao, Wang Han, Liu Xiao-Gang

机构信息

Department of Gastroenterology, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.

Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.

出版信息

Oncol Lett. 2016 Apr;11(4):2806-2814. doi: 10.3892/ol.2016.4319. Epub 2016 Mar 9.

DOI:10.3892/ol.2016.4319
PMID:27073556
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4812121/
Abstract

Yes-associated protein (YAP) is constitutively activated in numerous types of cancer, including gastric carcinoma. The aim of the present study was to investigate the effects of YAP silencing on proliferation, apoptosis, metastasis and angiogenesis in a gastric orthotopic implantation cancer model of severe combined immunodeficiency mice. Small-hairpin RNA (shRNA) targeting the YAP gene was employed to inhibit YAP expression. SGC7901 cells transfected with YAP shRNA demonstrated significantly decreased gastric cancer growth and metastasis in the orthotopic implantation mouse model. Silencing of YAP additionally promoted tumor cell apoptosis, and inhibited tumor cell proliferation and angiogenesis. Notably, YAP shRNA also downregulated the expression of TEA domain family member 1, cyclinD1, vascular endothelial growth factor and fibroblast growth factor-2. The results of the present study suggested that YAP may have a significant role in the proliferation, metastasis and angiogenesis of gastric cancer. RNA interference-mediated silencing of YAP may provide an opportunity to develop a novel treatment strategy for gastric cancer.

摘要

Yes相关蛋白（YAP）在包括胃癌在内的多种癌症类型中持续激活。本研究旨在探讨YAP沉默对严重联合免疫缺陷小鼠胃癌原位植入癌模型中增殖、凋亡、转移和血管生成的影响。采用靶向YAP基因的小发夹RNA（shRNA）抑制YAP表达。在原位植入小鼠模型中，用YAP shRNA转染的SGC7901细胞显示胃癌生长和转移显著降低。YAP沉默还促进肿瘤细胞凋亡，并抑制肿瘤细胞增殖和血管生成。值得注意的是，YAP shRNA还下调了TEA结构域家族成员1、细胞周期蛋白D1、血管内皮生长因子和成纤维细胞生长因子-2的表达。本研究结果表明，YAP可能在胃癌的增殖、转移和血管生成中起重要作用。RNA干扰介导的YAP沉默可能为开发新的胃癌治疗策略提供机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ab/4812121/c47d57679a73/ol-11-04-2806-g06.jpg
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The emerging roles of YAP and TAZ in cancer.YAP和TAZ在癌症中的新作用。
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Ki67 is a promising molecular target in the diagnosis of cancer (review).Ki67是癌症诊断中一个有前景的分子靶点（综述）。
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