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Published on: June 6, 2017
ZNF146 regulates cell cycle progression via TFDP1 and DEPDC1B in ovarian cancer cells
Ruixue Zhao1, Nana Song2, Xin Ning1
1Department of Gynaecology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P.R. China.
In Brief:
Aberration in cell cycle progression is one of the essential mechanisms underlying tumorigenesis, making regulators of cell cycle reasonable anti-cancer therapeutic targets. Here, we dissected the regulatory mechanism involving the novel axis ZNF146/TFDP1/DEPDC1B in the cell cycle in ovarian cancer.
Abstract:
Ovarian cancer (OC) is the third most common kind of gynecological tumor, in addition to being the most lethal. Transcription factor Dp-1 (TFDP1) functions as a binding partner for E2F transcription factors, and its target genes include those involved in DNA synthesis, cell cycle, and apoptosis. However, the regulatory role of TFDP1 in OC remains incompletely understood. This study aimed to investigate the role and mechanism of TFDP1 in OC. TFDP1 was highly expressed in the ovarian epithelial tissues of OC patients, and the expression of TFDP1 in OC cells was higher than that in normal ovarian epithelial cells. Silencing of TFDP1 inhibited the biological activity of OC cells and hindered cell cycle entry. Zinc finger protein 146 (ZNF146) knockdown induced cell cycle arrest at the G0/G1 phase and tumor growth by blocking TFDP1 transcription, which was overturned by ectopic expression of TFDP1. TFDP1 stimulated DEP domain-containing protein 1B (DEPDC1B) expression through transcriptional activation. DEPDC1B increased the proportion of OC cells in the G2/M phase and potentiated tumor malignant progression in nude mice inhibited by sh-ZNF146. Taken together, these findings demonstrate that ZNF146 participates in TFDP1/DEPDC1B activation and plays a vital role in the cell cycle in OC.
Insights
This study reveals a new pathway involving Zinc finger protein 146 (ZNF146), Transcription factor Dp-1 (TFDP1), and DEP domain-containing protein 1B (DEPDC1B) that regulates the cell cycle in ovarian cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Ovarian cancer (OC) is a lethal gynecological malignancy.
- Aberrant cell cycle progression is a hallmark of tumorigenesis.
- The role of Transcription factor Dp-1 (TFDP1) in OC requires further elucidation.
Purpose of the Study:
- To investigate the regulatory role and mechanism of TFDP1 in ovarian cancer.
- To identify novel regulators of the cell cycle in OC.
Main Methods:
- Analysis of TFDP1 expression in OC tissues and cells.
- Gene silencing experiments (ZNF146 knockdown, TFDP1 silencing).
- Assessment of cell cycle progression and tumor growth in vivo.
Main Results:
- TFDP1 expression is elevated in OC and promotes cell proliferation and cell cycle entry.
- ZNF146 knockdown inhibits OC cell growth by suppressing TFDP1 transcription.
- TFDP1 activates DEP domain-containing protein 1B (DEPDC1B) expression, promoting G2/M phase transition and tumor progression.
Conclusions:
- The ZNF146/TFDP1/DEPDC1B axis is a critical regulator of the cell cycle in ovarian cancer.
- Targeting this axis may offer novel therapeutic strategies for OC.
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