Abstract
We previously reported that the transcription factor Zinc Finger Protein 143 (ZNF143) regulates the expression of genes associated with cell cycle and cell division, and that downregulation of ZNF143 induces cell cycle arrest at G2/M. To assess the function of ZNF143 expression in the cell cycle, we established two cells with forced expression of ZNF143 derived from PC3 prostate cancer cell lines. These cell lines overexpress genes associated with cell cycle and cell division, such as polo-like kinase 1 (PLK1), aurora kinase B (AURKB) and some minichromosome maintenance complex components (MCM). However, the doubling time of cells with forced expression of ZNF143 was approximately twice as long as its control counterpart cell line. Analysis following serum starvation and re-seeding showed that PC3 cells were synchronized at G1 in the cell cycle. Also, ZNF143 expression fluctuated, and was at its lowest level in G2/M. However, PC3 cells with forced expression of ZNF143 synchronized at G2/M, and showed lack of cell cycle-dependent fluctuation of nuclear expression of MCM proteins. Furthermore, G2/M population of both cisplatin-resistant PCDP6 cells over-expressing ZNF143 (derived from PC3 cells) and cells with forced expression of ZNF143 was significantly higher than that of each counterpart, and the doubling time of PCDP6 cells is about 2.5 times longer than that of PC3 cells. These data suggested that fluctuations in ZNF143 expression are required both for gene expression associated with cell cycle and for cell division.
Highlights
IntroductionZinc finger protein 143 (ZNF143) is a transcription factor identified as a human homolog of Staf [1]
Zinc finger protein 143 (ZNF143) is a transcription factor identified as a human homolog of Staf [1]and is involved in the transcriptional regulation of snRNA and snRNA-type genes by RNA polymerase II or III [2,3]
We previously reported that knockdown of ZNF143 in PC3 prostate cancer cells reduces the cell proliferation rate, induces G2M cell cycle arrest, and results in downregulation of 41 genes associated with cell cycle and DNA replication [6]
Summary
Zinc finger protein 143 (ZNF143) is a transcription factor identified as a human homolog of Staf [1]. We have previously reported that knockdown of ZNF143 reduces cell proliferation and induces G2M cell cycle arrest. We found that ZNF143 knockdown resulted in the downregulation of 152 genes in PC3 human prostate cancer cells. Of these 152 genes, 41 (27%) were associated with cell cycle and DNA replication. We previously reported thatZNF143 expression is induced by DNA-damaging agents, and is overexpressed in cisplatin-resistant prostate cancer PC3 cell lines [7,8]. The proliferation of PC3 cells with forced expression of ZNF143 is much slower than that of its wild-type counterpart cell line, and nuclear expression of several MCMs between these cells is different. We hypothesize that the expression cycle of ZNF143 is associated with cell division
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