2. Academic Validation
  3. Ribosomal protein L6 suppresses hepatocellular carcinoma by modulating FBXO22-mediated p53 degradation

Ribosomal protein L6 suppresses hepatocellular carcinoma by modulating FBXO22-mediated p53 degradation

  • Cell Signal. 2025 Mar:127:111612. doi: 10.1016/j.cellsig.2025.111612.
Zhen Lei 1,  Yiming Luo 2,  Qinggang Fu 2,  Junli Lu 2,  Chao Wang 2,  Long Zhang 3,  Zhiwei Zhang 4
Affiliations

Affiliations

  • 1 Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Clinical Medicine Research Center for Hepatic Surgery of Hubei Province, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei 430030, PR China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang 832008, PR China.
  • 2 Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Clinical Medicine Research Center for Hepatic Surgery of Hubei Province, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei 430030, PR China.
  • 3 Department of Hepatopancreatobiliary Surgery, Ganzhou People's Hospital of Jiangxi Province (Ganzhou Hospital Afffliated to Nanchang University), Ganzhou 341000, PR China. Electronic address: zhanglong@mail.gzsrmyy.com.
  • 4 Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Clinical Medicine Research Center for Hepatic Surgery of Hubei Province, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei 430030, PR China. Electronic address: zwzhang@tjh.tjmu.edu.cn.
PMID: 39842528 DOI: 10.1016/j.cellsig.2025.111612
Abstract

The ribosomal protein L6 (RPL6) is significant in the progression of different Cancer types. However, its precise role in hepatocellular carcinoma (HCC) remains unclear. This research demonstrated that the expression levels of RPL6 are notably decreased in HCC tissues. The decreased expression of RPL6 is strongly linked to tumor size, the presence of vascular invasion, and a worse prognosis. Functional experiments revealed that the expression of RPL6 impedes the proliferation of HCC cells and the advancement of xenograft tumors. Mechanistically, we found that RPL6 binds to and is degraded by the E3 ubiquitin Ligase FBXO22, thereby inhibiting the polyubiquitination and subsequent degradation of p53 by FBXO22. The enhanced activity of p53 further contributes to cell growth inhibition. In contrast, the levels of p53 decreased significantly following RPL6 depletion, indicating that RPL6 is essential for the stabilization of p53. In summary, RPL6 inhibits the proliferation of HCC cells via the FBXO22/p53 signaling pathway, suggesting its potential as a biomarker and a therapeutic target for HCC.

Keywords

HCC; RPL6; Ubiquitination; p53.

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