title: Role of ZNF143 in tumor growth through transcriptional regulation of DNA replication and cell-cycle-associated genes.
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.
authors.affiliation: Department of Molecular Biology Otorhinolaryngology Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Wakasugi
authors.forename: Shohei
authors.initials: S
authors.lastname: Shimajiri
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
authors.forename: Eiji
authors.initials: E
authors.lastname: Kashiwagi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yasuniwa
authors.forename: Masaki
authors.initials: M
authors.lastname: Akiyama
authors.forename: Bin
authors.initials: B
authors.lastname: Han
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uchiumi
authors.forename: Tokuzo
authors.initials: T
authors.lastname: Arao
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Ryuta
authors.initials: R
authors.lastname: Yamazaki
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
mesh_terms: 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*
chemical_list: D015534:Trans-Activators; C114253:ZNF143 protein, human