Fig. 9

Schematic diagram of molecular mechanisms for the current study. Downregulation of MUC20 in PI-resistant MM cell lines and patients can predict the PI sensitivity and outcome of patients with MM. In addition, MUC20 attenuated PI resistance of MM cells by inducing cuproptosis in vitro and in vivo. Mechanistically, MUC20 triggered cuproptosis by inhibiting CDKN2A expression by hindering activation of MET in PI-resistant MM cells. Moreover, MUC20 suppressed MET activation by repressing IGF-1R lactylation in PI-resistant MM cells. In addition, eccDNA induced PI resistance by amplifying KIF3C to reduce MUC20 expression in MM.