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学科主题: 临床医学
题名:
Epigenetic inactivation of the candidate tumor suppressor gene ASC/TMS1 in human renal cell carcinoma and its role as a potential therapeutic target
作者: Liu, Qianling1,2; Jin, Jie1,2; Ying, Jianming3,4; Cui, Yun1,2; Sun, Mengkui1,2; Zhang, Lian1,2; Fan, Yu1,2; Xu, Ben1,2; Zhang, Qian1,2
关键词: ASC/TMS1 ; tumor suppressor ; DNA methylation ; renal cell carcinoma ; chemosensitivity
刊名: ONCOTARGET
发表日期: 2015-09-08
DOI: 10.18632/oncotarget.4256
卷: 6, 期:26, 页:22706-22723
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Cell Biology
研究领域[WOS]: Oncology ; Cell Biology
关键词[WOS]: CASPASE RECRUITMENT DOMAIN ; BREAST-CANCER CELLS ; NF-KAPPA-B ; COLORECTAL-CANCER ; DOWN-REGULATION ; CLEAR-CELL ; P53 ; APOPTOSIS ; ASC ; METHYLATION
英文摘要:

This study investigated the epigenetic alteration and biological function of the pro-apoptotic gene ASC/TMS1 in renal cell carcinoma. ASC/TMS1 was downregulated in five out of six RCC cell lines. A significant downregulation was also detected in sixty-seven paired renal tumors compared with adjacent non-cancerous tissues. The downregulation of ASC/TMS1 was correlated with promoter hypermethylation and could be restored with demethylation treatment. Re-expression of ASC/TMS1 in silenced RCC cell lines inhibited cell viability, colony formation, arrested cell cycle, induced apoptosis, suppressed cell invasion and repressed tumorigenicity in SCID mice. The antitumorigenic function of ASC/TMS1 in renal cancer was partially regulated by activation of p53 and p21 signaling. In addition, restoration of ASC/TMS1 sensitizes RCC cells to DNA damaging agents. Knockdown of ASC/TMS1 reduced DNA damaging agents-induced p53 activation and cell apoptosis. Moreover, ASC/TMS1 hypermethylation was further detected in 41.1% (83/202) of RCC tumors, but only 12% in adjacent non-cancerous tissues. ASC/TMS1 methylation was significantly correlated with higher tumor nuclear grade. In conclusion, ASC/TMS1 is a novel functional tumor suppressor in renal carcinogenesis. ASC/TMS1 tumor specific methylation may be a useful biomarker for designing improved diagnostic and therapeutic strategies for RCC.

语种: 英语
所属项目编号: 81272290
项目资助者: National Natural Science Foundation
WOS记录号: WOS:000362954800087
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62968
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

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作者单位: 1.Peking Univ, Dept Urol, Hosp 1, Beijing 100034, Peoples R China
2.Natl Res Ctr Genitourinary Oncol, Inst Urol, Beijing 100034, Peoples R China
3.Chinese Acad Med Sci, Dept Pathol, Inst Canc, Beijing 100021, Peoples R China
4.Chinese Acad Med Sci, Canc Hosp, Peking Union Med Coll PUMC, Beijing 100021, Peoples R China

Recommended Citation:
Liu, Qianling,Jin, Jie,Ying, Jianming,et al. Epigenetic inactivation of the candidate tumor suppressor gene ASC/TMS1 in human renal cell carcinoma and its role as a potential therapeutic target[J]. ONCOTARGET,2015,6(26):22706-22723.
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