An Evaluation of ZWINT as an mRNA 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 the ZWINT transcript 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 ZWINT mRNA isoform expression in PCa. We aim to fully categorize the alternative splicing regulation using antisense oligonucleotide (AON) interventions to force intron inclusion within the ZWINT transcript and study the influence of intron retention on cell behaviour.

This project has three main objectives:

1)    To determine the splicing factor landscape responsible for producing theZWINT_v1 isoform.

2)    To determine the consequences of intron inclusion on ZWINT_v1 transcript stabilityand cell behaviour.

3)    To design and validate AON interventions to influence tumour behaviour in prostatecancer 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.