Epigenetic identification, of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway
Epigenetic identification, of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway
复制标题
表观遗传学鉴定 ZNF545 通过激活 p53 信号通路作为多发性骨髓瘤的功能性肿瘤抑制因子
DOI：
10.1016/j.bbrc.2016.04.146
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发表时间：
2016-06-10
影响因子：
3.1
通讯作者：
Ren, Guosheng
中科院分区：
文献类型：
--
作者：
Fan, Yu;Zhan, Qian;Ren, Guosheng
The KRAB zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. (C) 2016 Elsevier Inc. All rights reserved.
