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Abstract：
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 β‑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 β‑catenin played a role in cell proliferation and drug resistance. Co‑transfection with small interfering (si)‑β‑catenin partially reversed the effect of NDRG3. This finding indicated that NDRG3 plays an important role in imatinib resistance and miR‑204‑5p and β‑catenin are involved in the biological behavior of NDRG3. The present results provide theoretical support for overcoming drug resistance in CML.
摘要：
慢性粒细胞白血病（CML）的伊马替尼耐药是一个临床问题。本研究探讨了N‑Myc下游调节基因3（NDRG3）在CML伊马替尼耐药中的作用。定量PCR显示NDRG3在CML患者中高表达。细胞计数试剂盒（CCK）-8实验证明，NDRG3促进K562CML细胞的增殖并增强伊马替尼耐药性。双荧光素酶实验显示microRNA(miR)-204-5p抑制NDRG3的表达，免疫荧光实验显示NDRG3促进β-连环蛋白在细胞核中的积累，从而增加下游耐药性和细胞周期相关因子（c‑Myc和MDR1）的表达。同时,细胞增殖实验表明β-catenin在细胞增殖和耐药中起作用。小干扰（si）β-catenin的共转染部分逆转了NDRG3的作用。这一发现表明NDRG3在伊马替尼耐药中起重要作用，miR‑204‑5p和β‑catenin参与NDRG3的生物学行为。本研究结果为克服CML的耐药性提供了理论支持。
