Role of ZNF143 in tumor growth through transcriptional regulation of DNA replication and cell-cycle-associated genes.
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.
Izumi
Hiroto
H
Department of Molecular Biology Otorhinolaryngology Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Wakasugi
Tetsuro
T
Shimajiri
Shohei
S
Tanimoto
Akihide
A
Sasaguri
Yasuyuki
Y
Kashiwagi
Eiji
E
Yasuniwa
Yoshihiro
Y
Akiyama
Masaki
M
Han
Bin
B
Wu
Ying
Y
Uchiumi
Takeshi
T
Arao
Tokuzo
T
Nishio
Kazuto
K
Yamazaki
Ryuta
R
Kohno
Kimitoshi
K
D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D047369:Chromatin Immunoprecipitation; D004261:DNA Replication / Q000502:physiology*; D005434:Flow Cytometry; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D018816:Genes, cdc; D006801:Humans; D007150:Immunohistochemistry; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D015534:Trans-Activators / Q000378:metabolism*
D015534:Trans-Activators; C114253:ZNF143 protein, human