OCT3/4 enhances tumor immune response by upregulating the TET1-dependent NRF2/MDM2 axis in bladder cancer

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Bladder cancer is a significant health concern with complex mechanisms of immune evasion.
• Understanding the molecular drivers of tumor immune escape is crucial for developing effective therapies.

Purpose of the Study:

• To investigate the role of Octamer-binding transcription factor 3/4 (OCT3/4) in bladder cancer immune escape.
• To elucidate the molecular pathway through which OCT3/4 influences tumor progression and immune evasion.

Main Methods:

• Quantification of OCT3/4, TET1, NRF2, and MDM2 expression in bladder cancer tissues and cells.
• Gain- and loss-of-function studies to assess the impact on cell migration, invasion, apoptosis, and tumorigenicity in vivo.
• Analysis of the regulatory interactions between OCT3/4, TET1, NRF2, and MDM2.

Main Results:

• Elevated expression of OCT3/4, TET1, NRF2, and MDM2 was observed in bladder cancer.
• OCT3/4 directly promotes TET1 expression, which in turn upregulates NRF2 via MLL recruitment.
• NRF2 enhances MDM2 expression, leading to accelerated tumor immune escape.
• OCT3/4 knockdown inhibited cell migration and invasion, induced apoptosis, and reduced tumor growth and immune escape in mice.

Conclusions:

• OCT3/4 promotes bladder cancer progression and immune escape by activating the TET1/NRF2/MDM2 signaling axis.
• Targeting OCT3/4 may represent a potential therapeutic strategy for bladder cancer by overcoming immune evasion.