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PMID:20860770
Citation |
Izumi, H, Wakasugi, T, Shimajiri, S, Tanimoto, A, Sasaguri, Y, Kashiwagi, E, Yasuniwa, Y, Akiyama, M, Han, B, Wu, Y, Uchiumi, T, Arao, T, Nishio, K, Yamazaki, R and Kohno, K (2010) Role of ZNF143 in tumor growth through transcriptional regulation of DNA replication and cell-cycle-associated genes. Cancer Sci. 101:2538-45 |
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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. |
Links |
PubMed Online version:10.1111/j.1349-7006.2010.01725.x |
Keywords |
Blotting, Western; Cell Line, Tumor; Cell Proliferation; Cell Separation; Chromatin Immunoprecipitation; DNA Replication/physiology; Flow Cytometry; Gene Expression; Gene Expression Regulation, Neoplastic; Genes, cdc; Humans; Immunohistochemistry; Neoplasms/genetics; Neoplasms/metabolism; Oligonucleotide Array Sequence Analysis; RNA Interference; Trans-Activators/metabolism |
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Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
GO:0045787: positive regulation of cell cycle |
ECO:0000314: |
P |
See Figure 2. |
complete | ||||
See also
References
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