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Updated: May 14, 2026
Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
Identification of transcription factors associated with castration-resistance: is the serum responsive factor a
Maria Prencipe1, Stephen F Madden, Amanda O'Neill
1UCD School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland. maria.prencipe@ucd.ie
Background:
Advanced prostate cancer is treated by hormone ablation therapy. However, despite an initial response, the majority of men relapse to develop castration-resistant disease for which there are no effective treatments. We have previously shown that manipulating individual proteins has only minor alterations on the resistant phenotype so we hypothesize that targeting the central transcription factors (TFs) would represent a better therapeutic approach.
Methods:
We have undertaken a transcriptomic analysis of gene expression differences between the androgen-dependent LNCaP parental cells and its castration-resistant Abl and Hof sublines, revealing 1,660 genes associated with castration-resistance. Using effective bioinformatic techniques, these transcriptomic data were integrated with TF binding sites resulting in a list of TFs associated with the differential gene expression observed.
Results:
Following validation of the gene-chip results, the serum response factor (SRF) was chosen for clinical validation and functional analysis due to its recent association with prostate cancer progression. SRF immunoreactivity in prostate tumor samples was shown for the first time to be associated with castration-resistance. SRF inhibition by siRNA and the small molecule inhibitor CCG-1423 resulted in decreased proliferation.
Conclusion:
SRF is a key TF by which resistant cells survive with depleted levels of androgens representing a target for therapeutic manipulation.
Insights
Targeting serum response factor (SRF), a key transcription factor (TF), offers a new therapeutic strategy for advanced prostate cancer. Inhibiting SRF reduces proliferation in castration-resistant prostate cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Advanced prostate cancer treatment relies on hormone ablation therapy, but most patients develop castration-resistant disease with limited therapeutic options.
- Previous attempts targeting individual proteins showed minimal impact on castration-resistant prostate cancer phenotype.
- Hypothesis: Targeting central transcription factors (TFs) may offer a more effective therapeutic strategy.
Purpose of the Study:
- To identify key transcription factors (TFs) driving castration-resistant prostate cancer.
- To evaluate the therapeutic potential of targeting identified TFs in prostate cancer.
Main Methods:
- Transcriptomic analysis of gene expression differences between androgen-dependent and castration-resistant prostate cancer cell lines.
- Bioinformatic integration of transcriptomic data with TF binding sites to identify relevant TFs.
- Clinical validation and functional analysis of the serum response factor (SRF) using immunohistochemistry, siRNA, and small molecule inhibitors.
Main Results:
- Identified 1,660 genes associated with castration-resistance in prostate cancer.
- Serum response factor (SRF) was identified as a key TF associated with castration-resistance.
- SRF inhibition via siRNA and CCG-1423 decreased proliferation in castration-resistant prostate cancer cells.
Conclusions:
- Serum response factor (SRF) is a crucial TF enabling prostate cancer cells to survive under androgen-depleted conditions.
- SRF represents a promising therapeutic target for overcoming castration-resistant prostate cancer.
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