2. Academic Validation
  3. USP8 promotes the tumorigenesis of intrahepatic cholangiocarcinoma via stabilizing OGT

USP8 promotes the tumorigenesis of intrahepatic cholangiocarcinoma via stabilizing OGT

  • Cancer Cell Int. 2024 Jul 7;24(1):238. doi: 10.1186/s12935-024-03370-w.
Guo Long 1 2,  Dong Wang 3,  Jianing Tang 1 2,  Kuan Hu 1 2,  Ledu Zhou 4 5
Affiliations

Affiliations

  • 1 Department of Liver Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • 2 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • 3 Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.
  • 4 Department of Liver Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. zhould@csu.edu.cn.
  • 5 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. zhould@csu.edu.cn.
PMID: 38973004 DOI: 10.1186/s12935-024-03370-w
Abstract

Ubiquitination was considered to be a crucial factor in intrahepatic cholangiocarcinoma (iCCA) development. Herein, we identified Ubiquitin-specific peptidase 8 (USP8) as a key regulator for promoting the tumorigenesis of iCCA cell via stabilizing OGT. USP8 was overexpressed in human tumor tissues and correlated with worse survival. Moreover, the mass spectrometry and co-immunoprecipitation analysis indicated that USP8 interacted with OGT. USP8 worked as a bona fide deubiquitylase of OGT. It stabilized OGT in a deubiquitylation activity-dependent manner. Meanwhile, DUB-IN3, the USP8 Inhibitor, could also restrain the malignancy of intrahepatic cholangiocarcinoma. In addition, USP8 depletion promoted the response of iCCA to pemigatinib. In conclusion, our findings pointed to a previously undocumented catalytic role for USP8 as a deubiquitinating Enzyme of OGT. The USP8-OGT axis could be a potential target for iCCA therapy.

Keywords

Intrahepatic cholangiocarcinoma; OGT; Pemigatinib; USP8; Ubiquitination.

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