RASSF5A, a candidate tumor suppressor, is epigenetically inactivated in esophageal squamous cell carcinoma
RASSF5A, a candidate tumor suppressor, is epigenetically inactivated in esophageal squamous cell carcinoma
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DOI：
10.1007/s10585-015-9693-6
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发表时间：
2015-01-01
影响因子：
4
通讯作者：
Dong, Zhiming
中科院分区：
文献类型：
--
作者：
Guo, Wei;Wang, Cong;Dong, Zhiming
由于选择性剪接和不同启动子的使用，RASSF 5至少存在三种异构体（RASSF 5A-RASSF 5C），它们可能在肿瘤发生中发挥不同的作用。本研究旨在检测RASSF 5 A、B和C在食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）中的作用，明确RASSF 5 A的关键CpG位点，为RASSF 5在ESCC发病机制中的作用提供更多信息。在食管癌细胞系中发现RASSF 5A的频繁沉默，而RASSF 5 B和RASSF 5C没有，并且RASSF 5A的沉默可以被5-Aza-dC或TSA处理逆转。RASSF 5A基因CpG岛1甲基化导致TE 13细胞表达沉默RASSF 5A基因mRNA和蛋白表达在食管鳞癌组织中均呈下降趋势，且与RASSF 5A基因CpG岛1甲基化状态有关。与RASSF 5A不同，RASSF 5 B和RASSF 5C在食管鳞癌组织中的表达无明显差异。RASSF 5C基因启动子区甲基化在食管鳞癌中也未见异常。RASSF 5A甲基化和蛋白表达与ESCC患者的生存独立相关。提示RASSF 5A基因通过CpG岛1甲基化失活在食管鳞癌的发生发展中起重要作用，RASSF 5A可能是一种功能性肿瘤抑制因子，并可作为食管鳞癌的预后生物标志物。
As a result of alternative splicing and differential promoter usage, RASSF5 exists in at least three isoforms (RASSF5A-RASSF5C), which may play different roles in tumorigenesis. The present study was to detect the role of RASSF5A, B and C in esophageal squamous cell carcinoma (ESCC) and clarify the critical CpG sites of RASSF5A, in order to clarify more information on the role of RASSF5 with regard to the pathogenesis of ESCC. Frequent silencing of RASSF5A but not RASSF5B and RASSF5C were found in esophageal cancer cell lines and the silencing of RASSF5A may be reversed by 5-Aza-dC or TSA treatment. The aberrant CpG island 1 methylation of RASSF5A induces silencing of its expression in TE13 cell line. Decreased mRNA and protein expression of RASSF5A was observed in ESCC tumor tissues and was associated with RASSF5A CpG island 1 methylation status. Unlike RASSF5A, expression variation of RASSF5B and RASSF5C was not found in ESCC tissues. Aberrant promoter methylation of RASSF5C was also not found in ESCC. RASSF5A methylation and protein expression were independently associated with ESCC patients' survival. These data indicated that the inactivation of RASSF5A through CpG island 1 methylation may play an important role in ESCC carcinogenesis, RASSF5A may be a functional tumor suppressor and may serve as a prognostic biomarker for ESCC.