2. Academic Validation
  3. PDLIM2 deficiency mediated by PBXIP1 promotes the proliferation of HCC cells through reducing the polyubiquitination and degradation of TRIM27

PDLIM2 deficiency mediated by PBXIP1 promotes the proliferation of HCC cells through reducing the polyubiquitination and degradation of TRIM27

  • Eur J Med Res. 2025 Dec 3;30(1):1208. doi: 10.1186/s40001-025-03488-1.
Xue Zhang 1 2,  Wengang Shan 1 2,  Qinghe Hu 1 2,  Kai Wu 1 2,  Mengxuan Ji 1 2,  Xiaotian Wang 1 2,  Zhiyi Liu 3 4,  Bin Zhang 5 6,  Hengliang Shi 7 8 9,  Kuan Cao 10 11
Affiliations

Affiliations

  • 1 Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, China.
  • 2 Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 3 Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, China. [email protected].
  • 4 Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • 5 Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, China. [email protected].
  • 6 Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • 7 Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, China. [email protected].
  • 8 Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • 9 Central Laboratory, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • 10 Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, China. [email protected].
  • 11 Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
PMID: 41340074 DOI: 10.1186/s40001-025-03488-1
Abstract

Accumulating evidences have indicated that PDZ and LIM domain 2 (PDLIM2) served as a critical tumor suppressor in hepatocellular carcinoma (HCC). However, the precise molecular mechanisms underlying its diminished protein expression in HCC pathogenesis remain poorly characterized. In this study, we revealed that PDLIM2 downregulation enhanced malignant proliferation of HCC cells. Mechanistically, PDLIM2 interacted with tripartite motif-containing protein 27 (TRIM27), facilitating its K27-linked polyubiquitination-mediated proteasomal degradation. This posttranslational modification consequently attenuated STAT3 signaling activation. Furthermore, we elucidated that pre-B-cell leukemia transcription factor-interacting protein 1 (PBXIP1) overexpression in HCC enhanced the polyubiquitination of PDLIM2 through the ubiquitin‒proteasome system, which was responsible for PDLIM2 protein destabilization in HCC. Collectively, our findings reveal that the PBXIP1-mediated posttranslational regulation of PDLIM2 contributes to its tumor-suppressive effects via the modulation of the TRIM27/STAT3 oncogenic axis during HCC progression.

Keywords

HCC; PBXIP1; PDLIM2; TRIM27; Ubiquitination.

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