UBA3 promotes the occurrence and metastasis of intrahepatic cholangiocarcinoma through MAPK signaling pathway

• UBA3 is highly expressed in intrahepatic cholangiocarcinoma (ICC) and promotes tumor proliferation, invasion, and migration via the MAPK signaling pathway. • Mechanistically, UBA3 exerts its oncogenic effects by modulating ANXA2 through the MAPK pathway, revealing a novel regulatory axis in ICC. • Bufalin, a natural compound, targets UBA3 and effectively inhibits ICC development and progression, suggesting a potential therapeutic strategy. • UBA3 emerges as a promising diagnostic biomarker and therapeutic target for ICC, addressing the urgent need for early detection and improved prognosis.