Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Department of Gastrointestinal Surgery, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Cell Signal. 2024 Sep;121:111279. doi: 10.1016/j.cellsig.2024.111279. Epub 2024 Jun 27.
The 26S proteasome non-ATPase regulatory subunit 11 is a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins, and PSMD11 plays a key role in the regulation of embryonic stem cell proteasome activity. However, the role of PSMD11 in hepatocellular carcinoma has not been studied. In this study, it was found that the expression of PSMD11 in HCC tissues was significantly higher than that in para-cancerous tissues, and was associated with poor prognosis. The results of in vitro experiments showed that PSMD11 knockdown could effectively inhibit the proliferation and apoptosis of hepatoma cell lines, and flow cytometry showed that the G0/G1 phase was significantly prolonged. Through protein spectrometry, immunoprecipitation and in vitro experiments, it was found that PSMD11 can promote the proliferation of hepatocellular carcinoma through regulating the ubiquitination of CDK4 and enhancing its protein stability. This study explores the mechanism of action of PSMD11 in hepatocellular carcinoma and provides new insights for the treatment of hepatocellular carcinoma.
26S 蛋白酶体非 ATP 酶调节亚基 11 是一种多蛋白复合物,参与泛素化蛋白的 ATP 依赖性降解,PSMD11 在调节胚胎干细胞蛋白酶体活性中发挥关键作用。然而,PSMD11 在肝细胞癌中的作用尚未得到研究。在这项研究中,发现 PSMD11 在 HCC 组织中的表达明显高于癌旁组织,并与不良预后相关。体外实验结果表明,PSMD11 敲低可有效抑制肝癌细胞系的增殖和凋亡,流式细胞术显示 G0/G1 期明显延长。通过蛋白质谱、免疫沉淀和体外实验,发现 PSMD11 可以通过调节 CDK4 的泛素化并增强其蛋白稳定性来促进肝癌的增殖。本研究探讨了 PSMD11 在肝细胞癌中的作用机制,为肝细胞癌的治疗提供了新的思路。