Inhibition of BAP1 Sensitizes Gastric Cancer Cells to 5-Fluorouracil by Promoting BIRC5 Degradation

Background/Objectives: Gastric cancer is an aggressive malignancy with poor prognosis, and acquired resistance to 5-fluorouracil (5-FU) remains a major therapeutic challenge. BRCA1-associated protein-1 (BAP1), a deubiquitinating enzyme, has been implicated in tumorigenesis; however, its role in gastric cancer and 5-FU resistance remains unclear. This study investigated the functional and molecular roles of BAP1 in gastric cancer progression and chemoresistance.

Methods

BAP1 expression and its association with patient prognosis were evaluated in gastric cancer tissues. The effects of BAP1 depletion on cancer cell proliferation, migration, invasion, and apoptosis were examined. The interaction between BAP1 and BIRC5 (Survivin) and the effects of BAP1-mediated deubiquitination on BIRC5 stability were investigated. The therapeutic effect of the BAP1 inhibitor iBAP-II was further assessed in 5-FU resistant gastric cancer cells.