HMGA2 regulates acute myeloid leukemia progression and sensitivity to daunorubicin via Wnt/β-catenin signaling

Yang,Shuo; Gu,Yueli; Wang,Genjie; Hu,Qingzhu; Chen,Shuxia; Wang,Yong; Zhao,Mingfeng

doi:10.3892/ijmm.2019.4229

HMGA2 regulates acute myeloid leukemia progression and sensitivity to daunorubicin via Wnt/β-catenin signaling

Authors:
- Shuo Yang
- Yueli Gu
- Genjie Wang
- Qingzhu Hu
- Shuxia Chen
- Yong Wang
- Mingfeng Zhao
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Affiliations: First Center Clinic College of Tianjin Medical University, Tianjin 300192, P.R. China, Department of Hematology, The First People's Hospital of Shangqiu, Shangqiu, Henan 476100, P.R. China, Department of Cardiology, The First People's Hospital of Shangqiu, Shangqiu, Henan 476100, P.R. China, Department of Hematology, Tianjin First Center Hospital, Tianjin 300192, P.R. China
Published online on: June 5, 2019 https://doi.org/10.3892/ijmm.2019.4229
Pages: 427-436
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute myeloid leukemia (AML) is a malignant disease with an increasing prevalence in adults and children. However, valuable molecular diagnostic research is rare. In the present study, plasmids silencing and overexpressing high‑mobility group AT‑hook 2 (HMGA2) were respectively transfected in HL60 and NB4 cells. The effects of HMGA2 on AML cell viability, apoptosis, migration and invasion were determined by preforming MTT, flow cytometry, wound scratch and Transwell assays, respectively. Genes associated with apoptosis and Wnt signaling were evaluated by reverse transcription‑quantitative (RT‑q)‑PCR and western blotting. AML cell sensitivity to daunorubicin (DNR) and the regulatory effects of the Wnt signaling pathway via HMGA2 following treatment with the agonist LiCl or antagonist XAV939 were detected by MTT, RT‑qPCR and western blot analysis. The results revealed that the expression of HMGA2 was elevated more so in HL60, KG1, U937, Kasumi‑1, THP‑1 and K562 cells than in NB4 cells. Silencing HMGA2 suppressed cell viability, migration and invasion, enhanced cell apoptosis and sensitivity to DNR, and almost restored the DNR inhibitory function that was promoted by LiCl treatment. In addition, low expression of HMGA2 attenuated X‑linked inhibitor of apoptosis and Bcl‑2 mRNA and protein levels, and upregulated the expression of Bax and cleaved‑caspase‑3. Furthermore, silencing HMGA2 not only decreased Wnt and non‑phospho‑β‑catenin expressions, but also partially reversed the increased expressions of these proteins induced by LiCl treatment. On the other hand, overexpression of HMGA2 exhibited the opposite results after transfection in NB4 cells. The results of the present study demonstrated that HMGA2 played important roles in driving AML progression and chemosensitivity in HL60 and NB4 cells, potentially by activating the Wnt/β‑catenin signaling pathway. Therefore, it was suggested that HMGA2 may be a promising molecular marker for AML diagnosis.

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