2. Academic Validation
  3. USP22-mediated deubiquitination of PTEN inhibits pancreatic cancer progression by inducing p21 expression

USP22-mediated deubiquitination of PTEN inhibits pancreatic cancer progression by inducing p21 expression

  • Mol Oncol. 2022 Mar;16(5):1200-1217. doi: 10.1002/1878-0261.13137.
Dianyun Ren 1 2,  Yan Sun 1 2,  Dan Li 3,  Heshui Wu 1 2,  Xin Jin 4
Affiliations

Affiliations

  • 1 Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Sino-German Laboratory of Personalized Medicine for Pancreatic Cancer, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Cardiovascular Medicine Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, China.
PMID: 34743406 DOI: 10.1002/1878-0261.13137
Abstract

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a dual lipid and protein Phosphatase. Multiple mechanisms contributing to the regulation of PTEN levels have been identified thus far, including post-translational modifications, epigenetic mechanisms, and transcriptional mechanisms. In the present study, we identified ubiquitin-specific peptidase 22 (USP22) as a novel deubiquitination-modifying Enzyme of PTEN. Furthermore, by inducing deubiquitination and inhibiting the degradation of PTEN, USP22 could induce cyclin-dependent kinase inhibitor 1A (CDKN1A, also symboled as p21) expression in pancreatic Cancer. Besides, MDM2 proto-oncogene (MDM2) inhibitor enhanced the antipancreatic Cancer effects of USP22 overexpression. In addition to its regulation of MDM2-tumor protein p53 (p53) signaling, we found that PTEN could induce p21 expression by interacting with ankyrin repeat and KH domain containing 1 (ANKHD1) and inhibiting ANKHD1 binding to the p21 promoter. Taken together, our results indicate that ANKHD1 and MDM2 might be novel therapeutic targets in pancreatic Cancer.

Keywords

ANKHD1; PTEN; USP22; p21; pancreatic cancer.

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