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学科主题: 基础医学
题名:
Genetic and epigenetic control of UNC5C expression in human renal cell carcinoma
作者: Lv, Dan1; Zhao, Wei1; Dong, Dong1; Qian, Xiao-Ping1; Zhang, Yu1; Tian, Xiao-Jun2; Zhang, Jun1
关键词: UNC5C ; Renal cell carcinoma ; Tumour suppressor ; DNA methylation ; Loss of heterozygosity
刊名: EUROPEAN JOURNAL OF CANCER
发表日期: 2011-09-01
DOI: 10.1016/j.ejca.2011.04.021
卷: 47, 期:13, 页:2068-2076
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: TUMOR-SUPPRESSOR GENE ; CLEAR-CELL ; METHYLATION ANALYSIS ; DNA METHYLATION ; RECEPTORS ; NETRIN-1 ; INACTIVATION ; CANCER ; HYPERMETHYLATION ; PROGRESSION
英文摘要:

Inappropriate gene silencing and subsequent promiscuous activity define the transformation of many solid tumours including renal cell carcinoma (RCC). Here, we report that UNC5C, one of the Netrin-1 receptors, was frequently inactivated in RCC cell lines and primary tumours. UNC5C protein was expressed in the proximal convoluted tubules of the human kidney, the presumed origin of clear cell RCC (ccRCC) and papillary RCC (pRCC). Compared to paired adjacent non-malignant tissues, both UNC5C mRNA and protein expression were significantly down-regulated in RCC. Immunohistochemical analysis showed that UNC5C was inactivated in 94.3% of the samples and the loss of UNC5C occurred at the early stage of RCC. Methylation specific PCR showed that UNC5C promoter was methylated in two renal carcinoma cell lines. Pharmacologic demethylation alone or in combination with inhibition of deacetylation dramatically induced UNC5C expression. Furthermore, bisulfite genomic sequencing (BGS) confirmed that dense methylation existed in UNC5C promoter. In paired tumour samples, UNC5C methylation was observed in 12 out of 44 patients (27.3%). Moreover, we analysed the loss of heterozygosity (LOH) of UNC5C in renal cell carcinoma, the LOH was observed in 27 out of 44 patients (61.4%). Finally, restoration of UNC5C expression suppressed the colony formation of renal carcinoma cells. In addition, UNC5C inhibited tumour cell proliferation, migration and enhanced chemosensitivity to cisplatin and etoposide. Therefore, UNC5C acts as a tumour suppressor in RCC and is down-regulated in RCC. Loss of heterozygosity and DNA methylation contribute to the inactivation of UNC5C in renal cell carcinoma. (C) 2011 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 30600734 ; 30972781
项目资助者: National Natural Science Foundation of China ; Scientific Research Foundation for Returned Scholars, Ministry of Education of China
WOS记录号: WOS:000295116600018
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54189
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Peking Univ, Dept Urol, Hosp 3, Beijing 100191, Peoples R China
2.Peking Univ, Dept Immunol, Sch Basic Med Sci, Key Lab Immunol,Minist Hlth,Hlth Sci Ctr, Beijing 100191, Peoples R China

Recommended Citation:
Lv, Dan,Zhao, Wei,Dong, Dong,et al. Genetic and epigenetic control of UNC5C expression in human renal cell carcinoma[J]. EUROPEAN JOURNAL OF CANCER,2011,47(13):2068-2076.
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