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Updated: Jul 15, 2026
An Orthotopic Bladder Tumor Model and the Evaluation of Intravesical saRNA Treatment
Published on: July 28, 2012
Are overexpressed alternative survivin transcripts in human bladder cancer suitable targets for siRNA-mediated in
1Department of Urology, Faculty of Medicine, Technical University of Dresden, D-01307 Dresden, Germany. daniela.wuttig@uniklinikum-dresden.de
Abstract:
In order to reduce side effects of survivin-inhibiting anticancer therapies, we determined the expression of the survivin transcripts survivin-wild-type (survivin-wt), survivin-DeltaEx3 (DeltaEx3) and survivin-2B (2B) in cryo-preserved tumor and non-malignant bladder tissues (18 tumor and 22 non-malignant samples, including 17 autologous tissue pairs) by quantitative PCR. Furthermore, we investigated the biological effects following specific inhibition of the alternative transcripts DeltaEx3 and 2B in bladder cancer (BCa) cells. In BCa and non-malignant bladder tissues survivin-wt was the quantitatively dominant transcript followed by DeltaEx3 and 2B. The mean mRNA expression of DeltaEx3 (0.37 vs. 0.06 zmol/amol GAPDH, respectively) and 2B (0.13 vs. 0.01 zmol/amol GAPDH, respectively) was significantly higher in BCa compared to non-malignant bladder tissues, indicating their accessibility for an expression inhibition in BCa cells. Effective and long-lasting small interfering RNA-mediated inhibition of one alternative survivin transcript caused lower cell growth reduction effects (apoptosis induction, cell cycle arrest, colony formation) compared to simultaneous inhibition of multiple survivin transcripts including survivin-wt. Inhibition of one alternative survivin transcript increased the apoptosis rate by 11% vs. 33-46% when reducing several survivin transcripts. We observed no G2/M arrest or reduction of cell colony formation after inhibiting one alternative survivin transcript. Reduction of cell viability by the chemotherapeutics cisplatin, mitomycin C or gemcitabine was stronger in combination with inhibition of several survivin transcripts than in combination with the reduction of one alternative survivin splice variant. Furthermore, reducing one alternative transcript caused chemosensitization to only one chemotherapeutic agent in contrast to inhibition of several survivin transcripts. Therefore, the alternative survivin transcripts DeltaEx3 and 2B do not represent reasonable targets for anticancer, at least BCa, treatment.
Insights
Alternative survivin transcripts DeltaEx3 and 2B are overexpressed in bladder cancer but do not represent viable anticancer targets. Inhibiting these alone yields limited effects compared to targeting multiple survivin transcripts.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Survivin is a key protein in cancer cell survival and proliferation.
- Alternative survivin transcripts, including survivin-DeltaEx3 (DeltaEx3) and survivin-2B (2B), are implicated in cancer progression.
- Targeting survivin is a strategy for anticancer therapies, but side effects are a concern.
Purpose of the Study:
- To determine the expression levels of survivin-wild-type (survivin-wt), DeltaEx3, and 2B transcripts in bladder cancer (BCa) tissues.
- To investigate the biological impact of inhibiting DeltaEx3 and 2B transcripts in BCa cells.
- To evaluate the potential of DeltaEx3 and 2B as therapeutic targets in BCa.
Main Methods:
- Quantitative PCR was used to analyze survivin transcript expression in tumor and non-malignant bladder tissues.
- Small interfering RNA (siRNA) was employed to specifically inhibit DeltaEx3 and 2B transcripts in BCa cells.
- Assays for apoptosis, cell cycle arrest, colony formation, and chemosensitivity were performed.
Main Results:
- Survivin-wt was the dominant transcript, with DeltaEx3 and 2B showing significantly higher expression in BCa tissues compared to non-malignant tissues.
- Inhibition of single alternative survivin transcripts (DeltaEx3 or 2B) resulted in minimal effects on cell growth, apoptosis, or cell cycle.
- Simultaneous inhibition of multiple survivin transcripts, including survivin-wt, led to more significant reductions in cell viability and enhanced chemosensitivity.
Conclusions:
- The alternative survivin transcripts DeltaEx3 and 2B are overexpressed in bladder cancer but are not effective monotherapy targets.
- Targeting multiple survivin transcripts, including survivin-wt, is more effective for reducing cancer cell growth and increasing chemosensitivity.
- DeltaEx3 and 2B are not recommended as standalone therapeutic targets for bladder cancer treatment.
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