NCAPD3 promotes prostate cancer progression by up-regulating EZH2 and MALAT1 through STAT3 and E2F1
Zuolei Jing1, Qianmei Liu1, Wanlin Xie1
1College of Life Sciences, Nanjing Normal University, Nanjing 210023, Jiangsu, China.
Abstract:
NCAPD3 is one of the non-SMC regulatory subunits of Condensin II, which is mainly responsible for the condensation and segregation of chromosomes during mitosis. However, its role in cancer especially in prostate cancer (PCa) and the molecular mechanism have not been clearly elucidated. Here, we find that NCAPD3 is high-expression and up-regulates the levels of EZH2 and MALAT1 in PCa. In detail, high expression of NCAPD3 increases the levels of transcription factor STAT3 and E2F1 and recruits more STAT3 and E2F1 to the promoter of EZH2 gene and more STAT3 to the promoter of MALAT1 gene, and then results in the increasing expression of both EZH2 and MALAT1 in PCa cells. In vitro and in vivo functional characterization reveals that overexpression of NCAPD3 enhances the growth of PCa cells, while knockdown of NCAPD3 impairs the growth of PCa cells. Together, our data demonstrate that NCAPD3 is a tumor-promoting factor which enhances the progression of PCa by up-regulating EZH2 and MALAT1.
Insights
Nuclear Cap-Binding Domain Protein 3 (NCAPD3) promotes prostate cancer (PCa) progression. High NCAPD3 expression up-regulates EZH2 and MALAT1, enhancing PCa cell growth.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Condensin II, a complex regulating chromosome structure, has subunits like NCAPD3.
- The role of NCAPD3 in prostate cancer (PCa) and its underlying molecular mechanisms remain unclear.
- Understanding NCAPD3's function is crucial for developing targeted PCa therapies.
Purpose of the Study:
- To investigate the role of NCAPD3 in prostate cancer (PCa) progression.
- To elucidate the molecular mechanisms by which NCAPD3 influences PCa development.
- To determine the relationship between NCAPD3, EZH2, and MALAT1 in PCa.
Main Methods:
- Analysis of NCAPD3 expression levels in PCa tissues.
- Investigated the effects of NCAPD3 overexpression and knockdown on PCa cell growth in vitro and in vivo.
- Examined the molecular interactions involving NCAPD3, STAT3, E2F1, EZH2, and MALAT1 using promoter recruitment assays.
Main Results:
- NCAPD3 is highly expressed in PCa and promotes tumor growth.
- High NCAPD3 expression increases STAT3 and E2F1 levels, leading to enhanced EZH2 and MALAT1 expression.
- Knockdown of NCAPD3 inhibits PCa cell proliferation, while overexpression enhances it.
Conclusions:
- NCAPD3 acts as a tumor promoter in prostate cancer.
- NCAPD3 enhances PCa progression by up-regulating EZH2 and MALAT1 expression.
- Targeting NCAPD3 may represent a novel therapeutic strategy for prostate cancer.
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