Role of ZNF143 in tumor growth through transcriptional regulation of DNA replication and cell-cycle-associated genes.
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| Abstract |
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.
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| Authors | Hiroto Izumi, Tetsuro Wakasugi, Shohei Shimajiri, Akihide Tanimoto, Yasuyuki Sasaguri, Eiji Kashiwagi, Yoshihiro Yasuniwa, Masaki Akiyama, Bin Han, Ying Wu, Takeshi Uchiumi, Tokuzo Arao, Kazuto Nishio, Ryuta Yamazaki, Kimitoshi Kohno |
| Journal | Cancer science (Cancer Sci) Vol. 101 Issue 12 Pg. 2538-45 (Dec 2010) ISSN: 1349-7006 [Electronic] England |
| PMID | 20860770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2010 Japanese Cancer Association. |
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