NCAPD3‐mediated AKT activation regulates prostate cancer progression
Abstract Despite therapeutic improvements in prostate cancer treatment, the recurrence and mortality rates are still high, and the underlying mechanisms still need further study. Non‐SMC Condensin II Complex Subunit D3 (NCAPD3) is a subunit of condensin II complex, mainly involved in the mitotic chr...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-02-01
|
| Series: | FASEB BioAdvances |
| Subjects: | |
| Online Access: | https://doi.org/10.1096/fba.2024-00073 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832098343238500352 |
|---|---|
| author | Yi Zhang Wanlin Xie Xicui Zong Yuanyuan Fang Jia Ren Zuolei Jing Yong Wei Shan Lu Qingyi Zhu Ping Liu |
| author_facet | Yi Zhang Wanlin Xie Xicui Zong Yuanyuan Fang Jia Ren Zuolei Jing Yong Wei Shan Lu Qingyi Zhu Ping Liu |
| author_sort | Yi Zhang |
| collection | DOAJ |
| description | Abstract Despite therapeutic improvements in prostate cancer treatment, the recurrence and mortality rates are still high, and the underlying mechanisms still need further study. Non‐SMC Condensin II Complex Subunit D3 (NCAPD3) is a subunit of condensin II complex, mainly involved in the mitotic chromosome condensation of cells. This study aimed to figure out the detailed mechanisms by which NCAPD3 contributed to prostate cancer development. Clinical samples and cell lines were used to measure the expression of genes by quantitative real‐time RT‐PCR (qRT‐PCR), Western‐blot assay (WB), immunohistochemistry (IHC), and immunofluorescence (IF). Chromatin immunoprecipitation quantitative PCR (ChIP‐qPCR) and dual‐luciferase reporter assays were examined to explore the interplays between molecules. CCK8, transwell, and wound‐healing assays were applied to perform cell proliferation and migration. A subcutaneous tumor xenograft model was constructed by injecting DU145‐Lv‐NCAPD3 cells and control cells into male BALB/c nude mice to confirm the result derived from in vitro assay. NCAPD3 increased STAT3 expression and phosphorylation in PCa cells, thereby enhancing STAT3 transcriptional activity to improve the levels of JAK2 and EZH2. This led to an increase in phosphorylation of AKT at Thr 308 and Ser 473 through JAK2/PI3K and EZH2/NSD2/mTORC2 pathways, respectively. Moreover, there was a positive mutual activation between STAT3 and JAK2, further enhanced by NCAPD3 to promote PCa progression. NCAPD3, as an oncogene, promoted PCa progression by phosphorylating and activating AKT, which suggests a novel functional pathway of NCAPD3 in promoting PCa progression. |
| format | Article |
| id | doaj-art-a309957c73dd48bda4640b74d0cd6efe |
| institution | Kabale University |
| issn | 2573-9832 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | FASEB BioAdvances |
| spelling | doaj-art-a309957c73dd48bda4640b74d0cd6efe2025-02-05T11:30:18ZengWileyFASEB BioAdvances2573-98322025-02-0172n/an/a10.1096/fba.2024-00073NCAPD3‐mediated AKT activation regulates prostate cancer progressionYi Zhang0Wanlin Xie1Xicui Zong2Yuanyuan Fang3Jia Ren4Zuolei Jing5Yong Wei6Shan Lu7Qingyi Zhu8Ping Liu9College of Life Sciences Nanjing Normal University Nanjing Jiangsu ChinaCollege of Life Sciences Nanjing Normal University Nanjing Jiangsu ChinaDepartment of Basic Medicine Nanjing University of Chinese Medicine Hanlin College Taizhou Jiangsu ChinaCollege of Life Sciences Nanjing Normal University Nanjing Jiangsu ChinaCollege of Life Sciences Nanjing Normal University Nanjing Jiangsu ChinaCollege of Life Sciences Nanjing Normal University Nanjing Jiangsu ChinaDepartment of Urology The Second Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu ChinaCollege of Life Sciences Nanjing Normal University Nanjing Jiangsu ChinaDepartment of Urology The Second Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu ChinaCollege of Life Sciences Nanjing Normal University Nanjing Jiangsu ChinaAbstract Despite therapeutic improvements in prostate cancer treatment, the recurrence and mortality rates are still high, and the underlying mechanisms still need further study. Non‐SMC Condensin II Complex Subunit D3 (NCAPD3) is a subunit of condensin II complex, mainly involved in the mitotic chromosome condensation of cells. This study aimed to figure out the detailed mechanisms by which NCAPD3 contributed to prostate cancer development. Clinical samples and cell lines were used to measure the expression of genes by quantitative real‐time RT‐PCR (qRT‐PCR), Western‐blot assay (WB), immunohistochemistry (IHC), and immunofluorescence (IF). Chromatin immunoprecipitation quantitative PCR (ChIP‐qPCR) and dual‐luciferase reporter assays were examined to explore the interplays between molecules. CCK8, transwell, and wound‐healing assays were applied to perform cell proliferation and migration. A subcutaneous tumor xenograft model was constructed by injecting DU145‐Lv‐NCAPD3 cells and control cells into male BALB/c nude mice to confirm the result derived from in vitro assay. NCAPD3 increased STAT3 expression and phosphorylation in PCa cells, thereby enhancing STAT3 transcriptional activity to improve the levels of JAK2 and EZH2. This led to an increase in phosphorylation of AKT at Thr 308 and Ser 473 through JAK2/PI3K and EZH2/NSD2/mTORC2 pathways, respectively. Moreover, there was a positive mutual activation between STAT3 and JAK2, further enhanced by NCAPD3 to promote PCa progression. NCAPD3, as an oncogene, promoted PCa progression by phosphorylating and activating AKT, which suggests a novel functional pathway of NCAPD3 in promoting PCa progression.https://doi.org/10.1096/fba.2024-00073AKTNCAPD3phosphorylationprostate cancerSTAT3 |
| spellingShingle | Yi Zhang Wanlin Xie Xicui Zong Yuanyuan Fang Jia Ren Zuolei Jing Yong Wei Shan Lu Qingyi Zhu Ping Liu NCAPD3‐mediated AKT activation regulates prostate cancer progression FASEB BioAdvances AKT NCAPD3 phosphorylation prostate cancer STAT3 |
| title | NCAPD3‐mediated AKT activation regulates prostate cancer progression |
| title_full | NCAPD3‐mediated AKT activation regulates prostate cancer progression |
| title_fullStr | NCAPD3‐mediated AKT activation regulates prostate cancer progression |
| title_full_unstemmed | NCAPD3‐mediated AKT activation regulates prostate cancer progression |
| title_short | NCAPD3‐mediated AKT activation regulates prostate cancer progression |
| title_sort | ncapd3 mediated akt activation regulates prostate cancer progression |
| topic | AKT NCAPD3 phosphorylation prostate cancer STAT3 |
| url | https://doi.org/10.1096/fba.2024-00073 |
| work_keys_str_mv | AT yizhang ncapd3mediatedaktactivationregulatesprostatecancerprogression AT wanlinxie ncapd3mediatedaktactivationregulatesprostatecancerprogression AT xicuizong ncapd3mediatedaktactivationregulatesprostatecancerprogression AT yuanyuanfang ncapd3mediatedaktactivationregulatesprostatecancerprogression AT jiaren ncapd3mediatedaktactivationregulatesprostatecancerprogression AT zuoleijing ncapd3mediatedaktactivationregulatesprostatecancerprogression AT yongwei ncapd3mediatedaktactivationregulatesprostatecancerprogression AT shanlu ncapd3mediatedaktactivationregulatesprostatecancerprogression AT qingyizhu ncapd3mediatedaktactivationregulatesprostatecancerprogression AT pingliu ncapd3mediatedaktactivationregulatesprostatecancerprogression |