MINDY1 promotes bladder cancer progression by stabilizing YAP.
Yongwen Luo1,2, Jun Zhou3, Jianing Tang2
1Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Cancer Cell International
|July 28, 2021
Summary
MINDY1 deubiquitylase stabilizes YAP in bladder cancer, promoting proliferation. Inhibiting MINDY1 or YAP offers a potential therapeutic strategy for bladder cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Bladder cancer is a common urological malignancy.
- The Hippo tumor suppressor pathway and its effector YAP are crucial in carcinogenesis.
- Mechanisms of abnormal YAP expression in bladder cancer require further elucidation.
Purpose of the Study:
- To investigate the role of MINDY1 as a deubiquitylase of YAP in bladder cancer.
- To explore the therapeutic potential of targeting the MINDY1-YAP interaction.
Main Methods:
- Western blot and real-time PCR to assess protein and gene expression.
- Cell viability assays (CCK8) and in vivo xenograft models.
- Protein stability, immunoprecipitation, and ubiquitination assays to study YAP regulation.
Main Results:
- MINDY1 was identified as a deubiquitylase that interacts with, deubiquitylates, and stabilizes YAP in bladder cancer cells.
- MINDY1 depletion reduced bladder cancer cell proliferation and YAP/TEAD target gene expression.
- YAP overexpression rescued the effects of MINDY1 depletion, confirming YAP's central role.
Conclusions:
- MINDY1 acts as a deubiquitinating enzyme for YAP in bladder cancer.
- This study reveals a novel catalytic role for MINDY1.
- Targeting MINDY1 presents a potential therapeutic strategy for bladder cancer.
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