CYLD regulates cell ferroptosis through Hippo/YAP signaling in prostate cancer progression

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Prostate cancer (PCa) is a prevalent malignancy in men, but its underlying molecular mechanisms remain unclear.
• Understanding PCa pathogenesis is crucial for developing effective therapeutic strategies.
• Deubiquitinating enzymes play significant roles in cellular processes, including cancer development.

Purpose of the Study:

• To investigate the role of CYLD, a deubiquitinating enzyme, in prostate cancer development and progression.
• To elucidate the molecular mechanisms by which CYLD affects PCa.
• To explore the potential of CYLD as a therapeutic target in PCa.

Main Methods:

• Analysis of CYLD expression in PCa tissues and correlation with clinicopathological features.
• In vitro and in vivo experiments to assess the effects of CYLD on PCa cell proliferation and ferroptosis.
• Mechanistic studies involving YAP ubiquitination, ACSL4 and TFRC mRNA transcription, and Hippo/YAP signaling pathway.
• Examination of CYLD, ACSL4, and TFRC expression correlation in human PCa specimens.

Main Results:

• CYLD expression was found to be downregulated in PCa tissues and inversely correlated with pathological grade and clinical stage.
• CYLD inhibited PCa cell proliferation and enhanced sensitivity to ferroptosis both in vitro and in vivo.
• CYLD suppressed YAP ubiquitination, leading to increased ACSL4 and TFRC mRNA transcription.
• CYLD expression positively correlated with ACSL4 and TFRC expression in human PCa specimens.

Conclusions:

• CYLD functions as a tumor suppressor gene in prostate cancer.
• CYLD promotes cell ferroptosis in PCa by regulating the Hippo/YAP signaling pathway.
• CYLD's mechanism involves suppressing YAP ubiquitination and promoting ACSL4/TFRC transcription, offering potential therapeutic avenues.