2. Academic Validation
  3. UBR1 promotes anaplastic thyroid carcinoma progression via stabilizing YAP through monoubiquitylation

UBR1 promotes anaplastic thyroid carcinoma progression via stabilizing YAP through monoubiquitylation

  • Sci Rep. 2024 Aug 22;14(1):19496. doi: 10.1038/s41598-024-70458-8.
Min Xia # 1,  Chen Liang # 1 2,  Yu Yuan 1,  Jiang Luo 1 3,  Yuxin Zeng 1,  Mini Zhang 1,  Jiawen Tang 1 3,  Ziyu Jiang 3,  Yan Gong 4 5,  Conghua Xie 6 7
Affiliations

Affiliations

  • 1 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
  • 2 Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
  • 3 Tumor Precision Diagnosis and Treatment Technology and Translational Medicine, Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
  • 4 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. yan.gong@whu.edu.cn.
  • 5 Tumor Precision Diagnosis and Treatment Technology and Translational Medicine, Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. yan.gong@whu.edu.cn.
  • 6 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. chxie_65@whu.edu.cn.
  • 7 Tumor Precision Diagnosis and Treatment Technology and Translational Medicine, Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. chxie_65@whu.edu.cn.
  • # Contributed equally.
PMID: 39174635 DOI: 10.1038/s41598-024-70458-8
Abstract

Anaplastic thyroid carcinoma (ATC) is a highly aggressive human malignancy without effective treatment. Yes-associated protein (YAP) is a critical effector of the Hippo pathway, which is essential in thyroid carcinogenesis. However, the underlying mechanisms of aberrant YAP expression in ATC are not completely understood. Ubiquitylation-related Enzyme siRNA screening identified the ubiquitin protein Ligase E3 component n-recognin 1 (UBR1) as a stabilizer of YAP in ATC cells. UBR1 deficiency reduced YAP protein levels and its target gene expression. UBR1 directly interacted with YAP and promoted its monoubiquitylation, competitively suppressing its polyubiquitylation and resulting in extended protein half-life. UBR1 depletion reduced ATC cell proliferation and migration in vitro. Xenograft tumor studies also suggested that UBR1 knockdown suppressed ATC cell growth in vivo. Furthermore, exogenous YAP expression partially reversed the inhibitive effects of UBR1 depletion on ATC cell proliferation and migration. Our studies demonstrated that UBR1 directly interacts with YAP and stabilized it in a monoubiquitylation-dependent manner, consequently promoting ATC tumorigenesis, suggesting that UBR1 might be a potentially therapeutic target for ATC treatment.

Figures
Products