Selinexor, a novel inhibitor for multiple myeloma (MM), faces limited research on resistance. Heterogeneous nuclear ribonucleoprotein U (hnRNPU) was identified as a regulator impacting MM’s response to selinexor. Comparing control knockdown (CTR-KD) and hnRNPU knockdown (hnR-KD) MM cells revealed increased selinexor-induced cell death in hnR-KD cells in vitro and in mice. Lower hnRNPU expression correlated with positive patient response to selinexor. hnRNPU’s role involves influencing LTV1, NMD3 localization, and mRNA translation of MDM2 and RAN, key factors in XPO1-mediated nuclear export. These findings suggest hnRNPU could serve as a potential marker for categorizing MM patients for Selinexor use.
