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A frequent somatic mutation in CD274 3'-UTR leads to protein over-expression in gastric cancer by disrupting miR-570 binding

icecream 添加于 2012-10-15 00:09 | 1027 次阅读 | 0 个评论

作者
Wang W, Sun J, Li F, Li R, Gu Y, Liu C, Yang P, Zhu M, Chen L, Tian W, Zhou H, Mao Y, Zhang L, Jiang J, Wu C, Hua D, Chen W, Lu B, Ju J, Zhang X
摘要
Inhibitory costimulatory molecule CD274 expresses in various cancers and contributes to cancer immune evasion by inhibiting T cell activation and proliferation, yet the regulatory mechanisms for CD274 overexpression in cancers are poorly understood. In this study, we discovered a novel mechanism of CD274 expression regulated by miR-570. A guanine-to-cytosine mutation at the 3'-UTR of CD274 mRNA led to CD274 overexpression by disrupting the miR-570 binding. The mutations were widely observed in cancers by sequencing of 276 gastrointestinal cancers (esophageal, gastric, colorectal, hepatocellular, and pancreatic cancers). This mutation was significantly associated with CD274 overexpression in gastric cancer (P = 1.44x10(-10)) and with the pathological features including differentiation grade, depth of tumor invasion, lymph node metastasis, and tumor-node-metastases (TNM) stage. These findings suggest a novel regulatory mechanism for CD274 overexpression in gastric cancer mediated by miR-570 and a somatic mutation in CD274 3'-UTR, and provide a new insight to gastric carcinogenesis.
详细资料
- 关键词: 3' Untranslated Regions/*genetics; Antigens, CD274/*genetics; Gene Expression Regulation, Neoplastic/genetics; Humans; Lymphatic Metastasis/genetics; MicroRNAs/*genetics; Mutation; Stomach Neoplasms/*genetics/pathology
- 文献种类: Journal Article
- 期刊名称: Human Mutation
- 期刊缩写: Hum Mutat
- 期卷页: 2012年第33卷第3期 480-484页
- 地址: Medical Biotechnology Institute, Stem Cell Research Laboratory of Jiangsu Province, Soochow University, Suzhou, China
- ISBN: 1059-7794
学科领域生物医药 » 预防卫生学
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