Targeting NPM1 inhibits proliferation and promotes apoptosis of hepatic progenitor cells via suppression of mTOR signalling pathway

• NPM1 is highly expressed in hepatic progenitor cells and cHCC-CCA tissues, and its expression is upregulated by IL6, a key cytokine in malignant transformation. • Knockdown of NPM1 suppresses proliferation and induces apoptosis in hepatic progenitor cells via inhibition of the mTOR signalling pathway and activation of apoptosis pathways. • The small-molecule inhibitor NSC348884, which disrupts NPM1 dimerization, effectively induces apoptosis in BEL-7402 cells and inhibits tumour growth in a xenograft model, suggesting a novel therapeutic strategy for cHCC-CCA. • Targeting NPM1 may offer a promising approach to prevent recurrence and improve outcomes in patients with cHCC-CCA.