NDRG3 regulates imatinib resistance by promoting β-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.

Automated summary

This study found that NDRG3 is highly expressed in patients with chronic myelogenous leukemia (CML), promoting cell proliferation and enhancing imatinib resistance. MiR-204-5p inhibits the expression of NDRG3, while beta-catenin plays a role in cell proliferation and drug resistance. These findings provide theoretical support for overcoming drug resistance in CML.