ODC1 Polyamine Metabolism Drives Prostate Cancer via AKT and Splicing

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Prostate cancer is an aggressive malignancy with a need for better biomarkers.
• The gene ODC1, encoding ornithine decarboxylase, is implicated in prostate cancer, but its precise role is unclear.

Purpose of the Study:

• To investigate the mechanistic role of ODC1 in prostate cancer progression.
• To analyze the effects of reduced ODC1 expression on prostate cancer cell behavior, gene expression, and splicing.

Main Methods:

• Development of a prostate cancer cell model with reduced ODC1 expression (knockdown).
• Assessment of cell growth, movement, and death.
• RNA sequencing to identify differentially expressed genes and alternative splicing events.

Main Results:

• Reduced ODC1 expression significantly inhibited cell growth and movement, while increasing cell death.
• RNA sequencing revealed widespread changes in gene expression (565 upregulated, 497 downregulated) and over 2000 alternative splicing events.
• Affected genes and splicing events were primarily linked to angiogenesis, cell adhesion, cell cycle regulation, and protein modification.
• Key genes (CAV1, ITGB1, BNIP3, YTHDF2) were associated with the AKT signaling pathway.

Conclusions:

• ODC1 plays a significant role in prostate cancer cell behavior by modulating gene expression and alternative splicing.
• ODC1 influences critical pathways including angiogenesis, cell adhesion, and the cell cycle.
• The AKT pathway and polyamine metabolism represent potential therapeutic targets for prostate cancer treatment.