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：Qianling Liu, Jie Jin, Jianming Ying, Yun Cui, Mengkui Sun, Lian Zhang, Yu Fan, Ben Xu, Qian Zhang · 发表于：Oncotarget · 年份：2015 · DOI：10.18632/oncotarget.4256 · 被引用次数：30 · 研究领域：Epigenetics and DNA Methylation、Cancer-related gene regulation、RNA modifications and cancer

// Qianling Liu 1 , Jie Jin 1 , Jianming Ying 2 , Yun Cui 1 , Mengkui Sun 1 , Lian Zhang 1 , Yu Fan 1 , Ben Xu 1 , Qian Zhang 1 1 Department of Urology, Peking University First Hospital and Institute of Urology, National Research Center for Genitourinary Oncology, Beijing 100034, China 2 Department of Pathology, Cancer Institute and Cancer Hospital, Peking Union Medical College (PUMC), Chinese Academy of Medical Sciences, Beijing 100021, China Correspondence to: Qian Zhang, e-mail: zhangqian@bjmu.edu.cn , zhangqianbmu@vip.sina.com Keywords: ASC/TMS1, tumor suppressor, DNA methylation, renal cell carcinoma, chemosensitivity Received: April 12, 2015      Accepted: May 23, 2015      Published: June 05, 2015 ABSTRACT 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 partiall...