TBX3 stimulates proliferation and stem cell self-renewal in bladder carcinoma

Histol Histopathol. 2023 Jan;38(1):65-72. doi: 10.14670/HH-18-496. Epub 2022 Jul 20.

Abstract

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.

MeSH terms

  • Carcinoma* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Self Renewal
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Neoplastic Stem Cells / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Transforming Growth Factor beta1
  • TBX3 protein, human
  • T-Box Domain Proteins