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MicroRNA-221 silencing predisposed human bladder cancer cells to undergo apoptosis induced by TRAIL

Qiang Lu1, Chao Lu, Guo-Ping Zhou

  • 1Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Urologic Oncology
|September 22, 2009
PubMed
Abstract

Insights

Silencing microRNA-221 (miRNA-221) in bladder cancer cells increases their susceptibility to TRAIL-induced apoptosis. This suggests miRNA-221 suppression is a potential therapeutic strategy for bladder cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Bladder cancer presents a significant therapeutic challenge, particularly in advanced stages, with limited survival rates.
  • MicroRNAs (miRNAs) are emerging as key regulators in cancer development, with specific miRNAs implicated in various malignancies.
  • miRNA-221 has been identified as potentially oncogenic, warranting investigation into its role in bladder cancer.

Purpose of the Study:

  • To investigate the therapeutic potential of silencing miRNA-221 in bladder cancer.
  • To determine the effect of miRNA-221 suppression on the chemosensitivity of bladder cancer cells to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand).

Main Methods:

  • Northern blot analysis was employed to quantify miRNA-221 expression in bladder cancer cell lines (T24, RT4) and normal urothelial cells.
  • Antisense oligonucleotides were used to silence miRNA-221 in T24 cells.
  • Flow cytometry assessed apoptosis induction by TRAIL in miRNA-221-silenced cells and analyzed cell cycle distribution.
  • Western blotting detected p27(kip1) protein levels in response to TRAIL treatment in silenced cells.

Main Results:

  • miRNA-221 was significantly upregulated in bladder cancer cells (T24, RT4) compared to normal urothelial cells.
  • Silencing miRNA-221 sensitized TRAIL-resistant T24 bladder cancer cells to TRAIL-induced apoptosis.
  • miRNA-221 suppression led to increased p27(kip1) protein levels and enhanced caspase-3 activation upon TRAIL treatment.

Conclusions:

  • Silencing miRNA-221 enhances TRAIL-induced apoptosis in human bladder cancer T24 cells.
  • These findings highlight the potential of miRNA-221 suppression as a novel therapeutic approach for bladder cancer treatment.

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