Retinoids and EZH2 inhibitors cooperate to orchestrate anti-oncogenic effects on bladder cancer cells

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• Bladder cancers with mutations in chromatin regulatory genes often oppose Polycomb-mediated repression, indicating EZH2 as a therapeutic target.
• The retinoic acid signaling pathway is crucial for urothelium development and homeostasis, with retinoids exhibiting anti-oncogenic properties.

Purpose of the Study:

• To investigate the combined therapeutic effects of targeting EZH2 and retinoic acid signaling in bladder cancer.
• To potentiate the therapeutic response through a coordinated targeting strategy.

Main Methods:

• Simultaneous targeting of EZH2 and retinoic acid signaling pathways.
• Assessment of cell viability, apoptosis, and cell cycle arrest.
• Characterization of anti-oncogenic transcriptional reprogramming via CHOP and endoplasmic reticulum stress response.
• Molecular mechanism investigation of EZH2-mediated gene repression.

Main Results:

• Co-targeting EZH2 and retinoic acid signaling induced a synergistic reduction in bladder cancer cell viability.
• The strategy led to increased apoptosis and cell cycle arrest in a coordinated manner.
• Transcriptional reprogramming centered on CHOP and endoplasmic reticulum stress was observed, with EZH2 repressing unfolded protein response genes.

Conclusions:

• Simultaneous targeting of EZH2 and retinoic acid signaling presents a promising strategy for bladder cancer treatment.
• This approach stimulates an anti-oncogenic profile by inducing synergistic cell death and cell cycle arrest.
• Novel bladder carcinoma treatments could involve combining retinoids with EZH2 inhibitors.