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Published on: May 14, 2016
A central role for TRPS1 in the control of cell cycle and cancer development
Lele Wu1, Yuzhi Wang1, Yan Liu2
1The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Science, Southeast University, Nanjing, PR China. Contributed equally to this work.
Abstract:
The eukaryotic cell cycle is controlled by a complex regulatory network, which is still poorly understood. Here we demonstrate that TRPS1, an atypical GATA factor, modulates cell proliferation and controls cell cycle progression. Silencing TRPS1 had a differential effect on the expression of nine key cell cycle-related genes. Eight of these genes are known to be involved in the regulation of the G2 phase and the G2/M transition of the cell cycle. Using cell synchronization studies, we confirmed that TRPS1 plays an important role in the control of cells in these phases of the cell cycle. We also show that silencing TRPS1 controls the expression of 53BP1, but not TP53. TRPS1 silencing also decreases the expression of two histone deacetylases, HDAC2 and HDAC4, as well as the overall HDAC activity in the cells, and leads to the subsequent increase in the acetylation of histone4 K16 but not of histone3 K9 or K18. Finally, we demonstrate that TRPS1 expression is elevated in luminal breast cancer cells and luminal breast cancer tissues as compared with other breast cancer subtypes. Overall, our study proposes that TRPS1 acts as a central hub in the control of cell cycle and proliferation during cancer development.
Insights
The study reveals that TRPS1 regulates cell cycle progression and proliferation. TRPS1 is elevated in luminal breast cancer, suggesting its role as a central hub in cancer development.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The eukaryotic cell cycle regulatory network is complex and not fully understood.
- TRPS1, an atypical GATA factor, has a poorly defined role in cell cycle control.
Purpose of the Study:
- To investigate the role of TRPS1 in cell cycle regulation and proliferation.
- To determine TRPS1's impact on key cell cycle genes and epigenetic modifiers.
- To assess TRPS1 expression in different breast cancer subtypes.
Main Methods:
- Gene silencing of TRPS1.
- Cell synchronization studies.
- Analysis of cell cycle-related gene expression.
- Assessment of histone deacetylase (HDAC) activity and histone acetylation.
- Comparison of TRPS1 expression in breast cancer tissues.
Main Results:
- TRPS1 silencing differentially affected nine key cell cycle genes, primarily those involved in G2 phase and G2/M transition.
- TRPS1 controls the expression of 53BP1 and decreases HDAC2 and HDAC4 expression, leading to increased histone H4 K16 acetylation.
- TRPS1 expression is significantly elevated in luminal breast cancer cells and tissues.
Conclusions:
- TRPS1 plays a crucial role in controlling cell cycle progression, particularly in the G2 phase.
- TRPS1 influences cell proliferation through modulation of cell cycle genes and epigenetic modifications.
- Elevated TRPS1 in luminal breast cancer suggests its potential as a therapeutic target and biomarker for this subtype.
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