The inhibitory effect of silencing CDCA3 on migration and proliferation in bladder urothelial carcinoma
Dexin Shen1, Yayun Fang2,3, Fenfang Zhou1
1Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Background:
CDCA3 is an important component of the E3 ligase complex with SKP1 and CUL1, which could regulate the progress of cell mitosis. CDCA3 has been widely identified as a proto-oncogene in multiple human cancers, however, its role in promoting human bladder urothelial carcinoma has not been fully elucidated.
Methods:
Bioinformatic methods were used to analyze the expression level of CDCA3 in human bladder urothelial carcinoma tissues and the relationship between its expression level and key clinical characteristics. In vitro studies were performed to validate the specific functions of CDCA3 in regulating cell proliferation, cell migration and cell cycle process. Alterations of related proteins was investigated by western blot assays. In vivo studies were constructed to validate whether silencing CDCA3 could inhibit the proliferation rate in mice model.
Results:
Bioinformatic analysis revealed that CDCA3 was significantly up-regulated in bladder urothelial carcinoma samples and was related to key clinical characteristics, such as tumor grade and metastasis. Moreover, patients who had higher expression level of CDCA3 tend to show a shorter life span. In vitro studies revealed that silencing CDCA3 could impair the migration ability of tumor cells via down-regulating EMT-related proteins such as MMP9 and Vimentin and inhibit tumor cell growth via arresting cells in the G1 cell cycle phase through regulating cell cycle related proteins like p21. In vivo study confirmed that silencing CDCA3 could inhibit the proliferation of bladder urothelial carcinoma cells.
Conclusions:
CDCA3 is an important oncogene that could strengthen the migration ability of bladder urothelial carcinoma cells and accelerate tumor cell growth via regulating cell cycle progress and is a potential biomarker of bladder urothelial carcinoma.
Insights
Cell division cycle associated 3 (CDCA3) acts as an oncogene in bladder cancer, promoting tumor cell growth and migration. Silencing CDCA3 inhibits proliferation and suggests its potential as a biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Cell division cycle associated 3 (CDCA3) is a proto-oncogene involved in cell mitosis.
- Its specific role in human bladder urothelial carcinoma (BUC) requires further elucidation.
Purpose of the Study:
- To investigate the role of CDCA3 in BUC progression.
- To analyze the relationship between CDCA3 expression and clinical characteristics in BUC patients.
Main Methods:
- Bioinformatic analysis of CDCA3 expression in BUC tissues.
- In vitro studies on cell proliferation, migration, and cell cycle.
- Western blot assays for protein alterations.
- In vivo studies using a mouse model.
Main Results:
- CDCA3 is significantly upregulated in BUC and correlates with tumor grade and metastasis.
- Higher CDCA3 expression is linked to reduced patient survival.
- Silencing CDCA3 impairs tumor cell migration by downregulating EMT markers (MMP9, Vimentin) and inhibits growth by arresting cells in G1 phase.
- In vivo studies confirm CDCA3 silencing suppresses BUC cell proliferation.
Conclusions:
- CDCA3 functions as an oncogene in BUC, enhancing cell migration and growth.
- CDCA3 regulates cell cycle progression and is a potential biomarker for BUC.
