An Evaluation of Retained intron splicing event as Therapeutic Target in Prostate Cancer

Previously in our team, Mou et al. carried out a comprehensive analysis of splicing patterns in three different prostate data sets. The study identified the reduced expression of a retained intron in a mitosis and chromosome segregation regulator as a single common factor among the tested sets, which correlated with poor PCa prognosis.

Therefore, this project was designed to evaluate the potential therapeutic role of modifying intron retention expression in PCa. We aim to fully categorize the alternative splicing regulation using antisense oligonucleotide (AON) interventions to force intron retention within the transcript and study the influence on cell behaviour.

This project has three main objectives:

1)    To determine the splicing factor landscape responsible for the intron retention.

2)    To determine the consequences of intron inclusion on transcript stability and cell behaviour.

3)    To design and validate AON interventions to influence tumour behaviour in prostate cancer models.

With this study, we hope we could identify a potential therapeutic target for Prostate cancer patients carrying this molecular profile and improve their prognosis.

Research conducted by PhD student Aysha Al Bulushi.