NDRG3 regulates imatinib resistance by promoting -catenin accumulation in the nucleus in chronic myelogenous leukemia

Imatinib resistance in chronic myelogenous leukemia (CML) is a clinical problem. The present study examined the role of N-Myc downstream regulatory gene 3 (NDRG3) in imatinib resistance in CML. Quantitative PCR demonstrated that NDRG3 was highly expressed in patients with CML. Cell Counting Kit (CCK)-8 experiments proved that NDRG3 promoted the proliferation of K562 CML cells and enhanced imatinib resistance. Dual-luciferase assay showed that microRNA (miR)-204-5p inhibited expression of NDRG3 and immunofluorescence experiments showed that NDRG3 promoted accumulation of beta-catenin in the nucleus, thereby increasing the expression of downstream drug resistance- and cell cycle-associated factors (c-Myc and MDR1). At the same time, cell proliferation experiments showed that beta-catenin played a role in cell proliferation and drug resistance. Co-transfection with small interfering (si)-beta-catenin partially reversed the effect of NDRG3. This finding indicated that NDRG3 plays an important role in imatinib resistance and miR-204-5p and beta-catenin are involved in the biological behavior of NDRG3. The present results provide theoretical support for overcoming drug resistance in CML.