Journal
CANCER SCIENCE
Volume 101, Issue 12, Pages 2538-2545Publisher
WILEY
DOI: 10.1111/j.1349-7006.2010.01725.x
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Funding
- Ministry for Education, Culture, Sports, Science and Technology of Japan [17016075]
- University of Occupational and Environmental Health (UOEH) Japan
- Yakult Co., Ltd., Tokyo, Japan
- Vehicle Racing Commemorative Foundation
- Grants-in-Aid for Scientific Research [17016075] Funding Source: KAKEN
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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).
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