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Published on: October 30, 2013
Depletion of CDC5L inhibits bladder cancer tumorigenesis
Ziwei Zhang1, Weipu Mao1, Longsheng Wang1
1Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P. R. China.
Abstract:
Cell division cycle 5-like (CDC5L) protein is a cell cycle regulator of the G2/M transition and has been reported to participate in the catalytic step of pre-messenger RNA (mRNA) splicing and DNA damage repair. Recently, CDC5L was also found to act as a candidate oncogene in osteosarcoma and cervical tumours. However, the role of CDC5L expression in bladder cancer remains unclear. Here, we analysed the expression and clinical significance of CDC5L in bladder cancer tissues. The expression of CDC5L in fresh bladder cancer tissues and paraffin-embedded slices was evaluated by western blot and immunohistochemistry, respectively. We found that CDC5L was highly expressed in bladder cancer. The expression of CDC5L was significantly associated with bladder cancer pathology grade and Ki67 expression. Univariate and multivariate analyses showed that high CDC5L expression was an independent prognostic factor for the survival of bladder cancer patients. To determine whether CDC5L could regulate the proliferation of bladder cancer cells, we transfected bladder cancer cells with an interfering RNA targeting CDC5L and then investigated cell proliferation with a cell counting kit (CCK)-8, flow cytometry assays, colony formation and xenograft assay analyses. Our results indicate that knockdown of CDC5L inhibits proliferation of bladder cancer cells. In addition, reduced expression of CDC5L induced apoptosis of bladder cancer cells and inhibited their migration, invasion and EMT. These findings suggest that CDC5L might play an important role in bladder cancer and thus be a promising therapeutic target of bladder cancer.
Insights
High expression of Cell division cycle 5-like (CDC5L) protein correlates with poor prognosis in bladder cancer. Reducing CDC5L inhibits cancer cell proliferation, migration, and invasion, suggesting CDC5L as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Cell division cycle 5-like (CDC5L) is involved in cell cycle regulation, mRNA splicing, and DNA repair.
- CDC5L has been identified as a potential oncogene in osteosarcoma and cervical cancers.
- The role of CDC5L in bladder cancer pathogenesis is currently unknown.
Purpose of the Study:
- To investigate the expression and clinical significance of CDC5L in bladder cancer.
- To explore the functional role of CDC5L in bladder cancer cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT).
Main Methods:
- Western blot and immunohistochemistry were used to evaluate CDC5L expression in bladder cancer tissues.
- Bladder cancer cells were transfected with CDC5L-targeting interfering RNA.
- Cell proliferation was assessed using CCK-8 assays, flow cytometry, colony formation, and xenograft models.
- Apoptosis, migration, invasion, and EMT were analyzed following CDC5L knockdown.
Main Results:
- CDC5L was found to be highly expressed in bladder cancer tissues.
- High CDC5L expression correlated significantly with higher tumor grade and Ki67 expression.
- High CDC5L expression served as an independent prognostic factor for patient survival.
- Knockdown of CDC5L suppressed bladder cancer cell proliferation, induced apoptosis, and inhibited migration, invasion, and EMT.
Conclusions:
- CDC5L plays a significant role in bladder cancer progression.
- CDC5L represents a promising therapeutic target for bladder cancer treatment.
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