Lei Zhen, Luo Yiming, Fu Qinggang, Lu Junli, Wang Chao, Zhang Long, Zhang Zhiwei
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.
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.
Cell Signal. 2025 Mar;127:111612. doi: 10.1016/j.cellsig.2025.111612. Epub 2025 Jan 21.
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.
核糖体蛋白L6（RPL6）在不同类型癌症的进展中具有重要意义。然而，其在肝细胞癌（HCC）中的具体作用仍不清楚。本研究表明，HCC组织中RPL6的表达水平显著降低。RPL6表达降低与肿瘤大小、血管侵犯的存在以及更差的预后密切相关。功能实验表明，RPL6的表达会阻碍HCC细胞的增殖以及异种移植肿瘤的进展。从机制上讲，我们发现RPL6与E3泛素连接酶FBXO22结合并被其降解，从而抑制FBXO22对p53的多聚泛素化及随后的降解。p53活性增强进一步有助于抑制细胞生长。相反，RPL6缺失后p53水平显著下降，表明RPL6对p53的稳定至关重要。总之，RPL6通过FBXO22/p53信号通路抑制HCC细胞的增殖，提示其作为HCC生物标志物和治疗靶点的潜力。
