Role of ZNF143 in tumor growth through transcriptional regulation of DNA replication and cell-cycle-associated genes
Role of ZNF143 in tumor growth through transcriptional regulation of DNA replication and cell-cycle-associated genes
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DOI：
10.1111/j.1349-7006.2010.01725.x
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发表时间：
2010-12-01
期刊：
影响因子：
5.7
通讯作者：
Kohno, Kimitoshi
中科院分区：
文献类型：
--
作者：
Izumi, Hiroto;Wakasugi, Tetsuro;Kohno, Kimitoshi
细胞周期受到多种机制的严格调控，以确保细胞分裂。除了控制细胞周期的E2F家族外，对细胞周期相关基因的转录调控知之甚少。在这里，我们发现一种转录因子，锌指蛋白143(ZNF143)，正向调节许多细胞周期相关基因，并在多种实体瘤中高表达。RNA干扰(RNAi)下调ZNF143基因在人前列腺癌PC3细胞中表达下调。在这些ZNF143靶基因中，有41个基因(27%)与细胞周期和DNA复制相关，包括细胞分裂周期6同源基因(CDC6)、Polo-like kinase1(PLK1)和微小染色体维持复合体成分(MCM)DNA复制蛋白。此外，ZNF143的RNAi可诱导G2/M期细胞周期停滞后的细胞凋亡。10株肺癌细胞株的细胞生长与ZNF143的细胞表达显著相关。我们的数据表明，ZNF143可能是细胞周期的主要调节者。我们的发现还表明，ZNF143是越来越多的有希望成为抗癌药物靶点的非癌基因之一。(《癌症科学》2010；101：2538-2545)。
The cell cycle is strictly regulated by numerous mechanisms to ensure cell division. The transcriptional regulation of cell-cycle-related genes is poorly understood, with the exception of the E2F family that governs the cell cycle. Here, we show that a transcription factor, zinc finger protein 143 (ZNF143), positively regulates many cell-cycle-associated genes and is highly expressed in multiple solid tumors. RNA-interference (RNAi)-mediated knockdown of ZNF143 showed that expression of 152 genes was downregulated in human prostate cancer PC3 cells. Among these ZNF143 targets, 41 genes (27%) were associated with cell cycle and DNA replication including cell division cycle 6 homolog (CDC6), polo-like kinase 1 (PLK1) and minichromosome maintenance complex component (MCM) DNA replication proteins. Furthermore, RNAi of ZNF143 induced apoptosis following G2/M cell cycle arrest. Cell growth of 10 lung cancer cell lines was significantly correlated with cellular expression of ZNF143. Our data suggest that ZNF143 might be a master regulator of the cell cycle. Our findings also indicate that ZNF143 is a member of the growing list of non-oncogenes that are promising cancer drug targets. (Cancer Sci 2010; 101: 2538-2545).