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学科主题临床医学
Epigenetic inactivation of the candidate tumor suppressor gene ASC/TMS1 in human renal cell carcinoma and its role as a potential therapeutic target
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
2015-09-08
DOI10.18632/oncotarget.4256
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
WOS记录号WOS:000362954800087
项目编号81272290
资助机构National Natural Science Foundation
引用统计
被引频次:10[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62968
专题北京大学第一临床医学院_泌尿外科
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
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GB/T 7714
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.
APA Liu, Qianling.,Jin, Jie.,Ying, Jianming.,Cui, Yun.,Sun, Mengkui.,...&Zhang, Qian.(2015).Epigenetic inactivation of the candidate tumor suppressor gene ASC/TMS1 in human renal cell carcinoma and its role as a potential therapeutic target.ONCOTARGET,6(26),22706-22723.
MLA Liu, Qianling,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".ONCOTARGET 6.26(2015):22706-22723.
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