WWOX Modulates ROS-Dependent Senescence in Bladder Cancer

Area of Science:

• Oncology
• Molecular Biology
• Cellular Senescence

Background:

• WW domain-containing oxidoreductase (WWOX) is a tumor suppressor gene frequently lost in cancers.
• Reactive oxygen species (ROS) are critical signaling molecules in inducing cell senescence.

Purpose of the Study:

• To investigate the role of WWOX in regulating ROS and cell senescence.
• To explore the mechanism of WWOX in bladder cancer progression.

Main Methods:

• Utilized AY-27 rat bladder tumor cell line and F344 orthotopic bladder tumor models.
• Employed WWOX-overexpressing lentivirus (LV-WWOX) to assess senescence induction.
• Analyzed senescence markers, ROS generation, and cell cycle regulators (p21/p27).

Main Results:

• LV-WWOX significantly induced cellular senescence, including SASP formation, enlarged morphology, and SA-β-Gal staining.
• WWOX-induced senescence was dependent on increased ROS generation, activating p21/p27.
• LV-WWOX inhibited tumor size by 30.49% in vivo by activating cellular senescence and enhancing p21 expression.

Conclusions:

• WWOX acts as a pro-senescence gene in bladder cancer through ROS induction.
• WWOX demonstrates therapeutic potential for bladder cancer by inhibiting tumor growth.
• Further research into WWOX's therapeutic implications in bladder cancer is warranted.