title: A frequent somatic mutation in CD274 3'-UTR leads to protein over-expression in gastric cancer by disrupting miR-570 binding.
abstract: 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 = 1.44×10(-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.
authors.affiliation: Medical Biotechnology Institute, Stem Cell Research Laboratory of Jiangsu Province, Soochow University, Suzhou, China.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Yongping
authors.initials: Y
authors.lastname: Gu
authors.forename: Cuiping
authors.initials: C
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.forename: Lujun
authors.initials: L
authors.lastname: Chen
authors.forename: Wenyan
authors.initials: W
authors.lastname: Tian
authors.forename: Huan
authors.initials: H
authors.lastname: Zhou
authors.forename: Yong
authors.initials: Y
authors.lastname: Mao
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Jingting
authors.initials: J
authors.lastname: Jiang
authors.forename: Changping
authors.initials: C
authors.lastname: Wu
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
authors.forename: Weichang
authors.initials: W
authors.lastname: Chen
authors.forename: Binfeng
authors.initials: B
authors.lastname: Lu
authors.forename: Jingfang
authors.initials: J
authors.lastname: Ju
authors.forename: Xueguang
authors.initials: X
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D060890:B7-H1 Antigen / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D035683:MicroRNAs