COPB2通过调控YAP1核转位促进肝细胞癌进展。
COPB2 promotes hepatocellular carcinoma progression through regulation of YAP1 nuclear translocation.
作者信息
Wu Biao, Guo Xianlin, Wu Zhishi, Chen Liang, Zhang Suqing
机构信息
Department of General Surgery, Changhai Hospital, Second (Navy) Military Medical University, Shanghai, 200433, China.
Department of General Surgery, Zhengzhou First People's Hospital, Zhengzhou, 450000, China.
出版信息
Oncol Res. 2025 Mar 19;33(4):975-988. doi: 10.32604/or.2025.058085. eCollection 2025.
OBJECTIVES
Although Yes-associated protein 1 (YAP1) is an important oncogene in hepatocellular carcinoma (HCC) progression, its nuclear localization prevents it from being considered a potential therapeutic target. Recently, studies have reported that coatomer protein complex subunit beta 2 (COPB2) also plays a critical role in HCC development; however its mechanism of action is unclear. This study aimed to investigate the role of COPB2 and YAP1 in the progression of HCC and to elucidate the underlying mechanisms.
METHODS
COPB2 and YAP1 expression in HCC tissues were first analyzed by database searches and immunohistochemistry. Nomogram and artificial neural network models were established based on COPB2 and YAP1 expression. Cell proliferation was detected by cell counting kit-8 and clone formation assay, while cell migration and invasion were assessed using Transwell assays. Finally, the potential mechanisms underlying COPB2 regulation of YAP1 nuclear translocation were explored by immunofluorescence assay and Western blot.
RESULTS
COPB2 combined with YAP1 expression was associated with overall postoperative survival in HCC patients and was an independent prognostic factor. High expression of both COPB2 and YAP1 in patients may reduce the efficacy of postoperative transarterial chemoembolization therapy. experiments revealed that COPB2 affected the sensitivity of HCC cells to Cisplatin (DDP) by regulating YAP1 nuclear translocation.
CONCLUSIONS
Our findings suggest that COPB2/YAP1 affects the drug sensitivity of HCC cells to DDP and that targeting COPB2/YAP1 may be a promising strategy for the precision treatment of HCC.
目的
尽管Yes相关蛋白1(YAP1)在肝细胞癌(HCC)进展中是一种重要的癌基因,但其核定位使其无法被视为潜在的治疗靶点。最近,有研究报道衣被蛋白复合物亚基β2(COPB2)在HCC发展中也起关键作用;然而其作用机制尚不清楚。本研究旨在探讨COPB2和YAP1在HCC进展中的作用,并阐明其潜在机制。
方法
首先通过数据库检索和免疫组织化学分析HCC组织中COPB2和YAP1的表达。基于COPB2和YAP1的表达建立列线图和人工神经网络模型。采用细胞计数试剂盒-8和克隆形成试验检测细胞增殖,同时使用Transwell试验评估细胞迁移和侵袭。最后,通过免疫荧光试验和蛋白质免疫印迹法探索COPB2调节YAP1核转位的潜在机制。
结果
COPB2与YAP1的联合表达与HCC患者术后总生存期相关,是一个独立的预后因素。患者中COPB2和YAP1的高表达可能会降低术后经动脉化疗栓塞治疗的疗效。实验表明,COPB2通过调节YAP1核转位影响HCC细胞对顺铂(DDP)的敏感性。
结论
我们的研究结果表明,COPB2/YAP1影响HCC细胞对DDP的药物敏感性,靶向COPB2/YAP1可能是HCC精准治疗的一种有前景的策略。