TBX3 stimulates proliferation and stem cell self-renewal in bladder carcinoma
Lifu Huang1,2, Wenfei Shao2,3, Xiaohong Wang2,4
1Department of Urology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai City, Zhejiang Province, China.
Background:
With the change of people's lifestyle in recent years, bladder carcinoma has been the second leading cause of death for men. Nevertheless, surgical results of bladder carcinoma are unsatisfying with recurrence and distant metastasis. Therefore, it is urgent to find a new target for bladder carcinoma treatment.
Methods:
The protein and mRNA expression levels of TBX3 in bladder carcinoma tissue samples and cells were tested using western blot and qRT-PCR assays, respectively. Cancer stem cells (CSCs) were separated with immunomagnetic beads. Expression levels of cell stemness-associated proteins CD44, CD24 and ESA in T24 CSCs and T24 cells were detected by western blot assay. Cell self-renewal ability was detected by stem cell sphere formation assay. CCK-8 and colony formation assays examined cell viability and proliferation. Cell apoptotic level was examined by flow cytometry.
Results:
Elevated TBX3 expression in bladder carcinoma stimulated cell proliferation and inhibited cell apoptosis. Stemness-related proteins and TBX3 were highly expressed in T24 CSCs relative to those in normal bladder carcinoma cells. In addition, TBX3 promoted stem cell self-renewal and inhibited cell apoptosis. Finally, qRT-PCR, western blot and cell sphere formation assays revealed that the potential role of TGF-β1 in the regulation of TBX3.
Conclusion:
TBX3, mediated by TGF-β1, can promote bladder carcinoma cell proliferation, inhibit apoptosis, and enhance cell stemness. Hence, TBX3 is a potential target to stem cells of bladder carcinoma.
Insights
TBX3, a gene influenced by TGF-β1, fuels bladder carcinoma growth and stemness while hindering apoptosis. Targeting TBX3 offers a promising strategy for bladder cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Bladder carcinoma is a leading cause of cancer death in men, with high rates of recurrence and metastasis after surgery.
- Current treatments for bladder carcinoma have limitations, necessitating the identification of novel therapeutic targets.
Purpose of the Study:
- To investigate the role of TBX3 in bladder carcinoma.
- To explore the potential of TBX3 as a therapeutic target for bladder cancer.
Main Methods:
- Assessed TBX3 protein and mRNA expression in bladder carcinoma tissues and cells via Western blot and qRT-PCR.
- Isolated cancer stem cells (CSCs) and analyzed stemness-associated proteins (CD44, CD24, ESA).
- Evaluated cell proliferation, apoptosis, and self-renewal capabilities using CCK-8, colony formation, and sphere formation assays.
Main Results:
- Elevated TBX3 expression correlated with increased bladder carcinoma cell proliferation and decreased apoptosis.
- TBX3 and stemness markers were highly expressed in bladder cancer stem cells.
- TBX3 promoted CSC self-renewal and inhibited apoptosis, with TGF-β1 identified as a regulator of TBX3.
Conclusions:
- TBX3, regulated by TGF-β1, drives bladder carcinoma cell proliferation, inhibits apoptosis, and enhances stemness.
- TBX3 represents a potential therapeutic target for bladder cancer, particularly targeting cancer stem cells.
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