Prostate cancer (PCa) poses a significant health threat to males, and research has shown that fish oil (FO) can impede PCa progression by activating multiple mitochondria-related pathways. Our research is focused on investigating the impact of FO on succinylation, a posttranslational modification that is closely associated with mitochondria in PCa cells. This study employed a mass spectrometry-based approach to investigate succinylation in PCa cells. Bioinformatics analysis of these succinylated proteins identified glutamic-oxaloacetic transaminase 2 (GOT2) protein as a key player in PCa cell proliferation. Immunoprecipitation and RNA interference technologies validated the functional data. Further analyses revealed the significance of GOT2 protein in regulating nucleotide synthesis by providing aspartate, which is critical for the survival and proliferation of PCa cells. Our findings suggest that FO-dependent GOT2 succinylation status has the potential to inhibit building block generation. This study lays a solid foundation for future research into the role of succinylation in various biological processes. This study highlights the potential use of FO as a nutrition supplement for managing and slowing down PCa progression.
© 2023 Jiang et al.