ODC1 Polyamine Metabolism Drives Prostate Cancer via AKT and Splicing.

Prostate cancer is an aggressive disease with limited quantifiable biomarkers. One gene of interest is ODC1, which encodes ornithine decarboxylase, the rate-limiting enzyme converting ornithine to putrescine in polyamine metabolism. Although ODC1 is known to be involved in prostate cancer development, exactly how it drives the disease mechanistically is not fully understood. To explore this, we created a prostate cancer cell model with reduced ODC1 expression and examined its effects on tumour behaviours. Knocking down ODC1 significantly slowed cell growth and movement while increasing cell death. Using RNA sequencing, we identified over one thousand differentially expressed genes, with 565 upregulated and 497 downregulated, primarily linked to angiogenesis and cell adhesion. We also found more than two thousand alternative splicing events connected to cell cycle regulation and protein modification. Notably, genes including CAV1, ITGB1, BNIP3, and YTHDF2 were associated with the AKT signalling pathway, suggesting a functional link between ODC1 activity and cancer progression. These results indicate that ODC1 influences prostate cancer cell behaviour by regulating both gene expression and splicing, particularly affecting pathways involved in angiogenesis, adhesion, and the cell cycle. This points to the AKT pathway and polyamine metabolism as potentially valuable targets for future prostate cancer therapies.