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.

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.

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. In vitro experiments revealed that COPB2 affected the sensitivity of HCC cells to Cisplatin (DDP) by regulating YAP1 nuclear translocation.

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.