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

Oncol Rep. 2023 Aug;50(2):152. doi: 10.3892/or.2023.8589. Epub 2023 Jun 23.

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.

Keywords: N‑Myc downstream regulatory gene 3; chronic myelogenous leukemia; imatinib; microRNA‑204‑5p; β‑catenin.

MeSH terms

  • Humans
  • Imatinib Mesylate / pharmacology
  • Imatinib Mesylate / therapeutic use
  • Intracellular Signaling Peptides and Proteins
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • beta Catenin / genetics

Substances

  • Imatinib Mesylate
  • beta Catenin
  • MicroRNAs
  • NDRG3 protein, human
  • Intracellular Signaling Peptides and Proteins
  • MIRN204 microRNA, human

Grants and funding

The present study was supported by The Support Plan for Youth Entrepreneurship and Technology of Colleges and Universities in Shandong (grant no. 2019KJK014), The National Natural Science Foundation of China (grant nos. 81800169 and 82002604), The Shandong Science and Technology Committee (grant nos. ZR2019MH022, ZR2020QH221 and ZR2020KH015), The Shandong Province Taishan Scholar Project (grant no. ts201712067), The Foundation of Binzhou Medical University (grant no. BY2021LCX04) and The Shandong Province Yantai Science and Technology Project (grant no. 2022YD075).