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双调蛋白聚糖(DCN)缺乏通过下调P21和E-钙黏蛋白促进肾细胞癌的生长和转移。

DCN deficiency promotes renal cell carcinoma growth and metastasis through downregulation of P21 and E-cadherin.

作者信息

Xu Yongcan, Xia Qiuyuan, Rao Qiu, Shi Shanshan, Shi Qunli, Ma Henghui, Lu Zhenfeng, Chen Hui, Zhou Xiaojun

机构信息

Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China.

Department of General Surgery, Huzhou Central Hospital, Huzhou, China.

出版信息

Tumour Biol. 2016 Apr;37(4):5171-83. doi: 10.1007/s13277-015-4160-1. Epub 2015 Nov 7.

Abstract

Decorin (DCN), as an important component of the extracellular matrix (ECM), is a small leucine-rich proteoglycan and synthesized by fibroblasts. Although DCN is dysregulated in numerous cancer types, limited data are available on the expression level and important role of DCN proteins in renal cell carcinoma (RCC). In our study, we examined the expression patterns of DCN messenger RNA (mRNA) in RCCs through the Oncomine database and DCN protein in 94 RCC specimens by immunohistochemistry (IHC). The results revealed that DCN expression was decreased in cancerous tissues compared to adjacent noncancerous tissues and was highly correlated to tumor size. Then, via gain-of-function analyses, DCN overexpression could inhibit RCC cell proliferation and metastasis in vitro and vivo. At the mechanism level, we found that an ectopic expression of DCN significantly upregulated P21 and E-cadherin expression. Altogether, these results revealed that DCN is a tumor suppressor in RCC, and it could serve as a potential therapeutic target in patients with RCC.

摘要

核心蛋白聚糖(DCN)作为细胞外基质(ECM)的重要组成部分,是一种富含亮氨酸的小分子蛋白聚糖,由成纤维细胞合成。尽管DCN在多种癌症类型中表达失调,但关于DCN蛋白在肾细胞癌(RCC)中的表达水平和重要作用的数据有限。在我们的研究中,我们通过Oncomine数据库检测了RCC中DCN信使核糖核酸(mRNA)的表达模式,并通过免疫组织化学(IHC)检测了94例RCC标本中DCN蛋白的表达。结果显示,与相邻的非癌组织相比,癌组织中DCN表达降低,且与肿瘤大小高度相关。然后,通过功能获得分析,DCN过表达可在体外和体内抑制RCC细胞增殖和转移。在机制层面,我们发现DCN的异位表达显著上调了P21和E-钙黏蛋白的表达。总之,这些结果表明DCN是RCC中的一种肿瘤抑制因子,它可能成为RCC患者潜在的治疗靶点。

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