MicroRNA‑144 targets APP to regulate AML1/ETO+ leukemia cell migration via the p‑ERK/c‑Myc/MMP‑2 pathway

  • Authors:
    • Ling Jiang
    • Wei Meng
    • Guopan Yu
    • Changxin Yin
    • Zhixiang Wang
    • Libin Liao
    • Fanyi Meng
  • View Affiliations

  • Published online on: June 14, 2019     https://doi.org/10.3892/ol.2019.10477
  • Pages: 2034-2042
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Abstract

Extramedullary infiltration (EMI) is common in patients with acute myeloid leukemia (AML) and is closely associated with the prognosis of disease. We previously reported that patients carrying the AML1/ETO (A/E) fusion gene and expressing the amyloid precursor protein (APP) tended to develop EMI, and had a poor prognosis. In the present study, the relapse‑free survival (RFS) time and overall survival (OS) time were significantly lower in patients with EMI. The results demonstrated that the EMI incidence was significantly higher (P<0.05), while the RFS and OS rates were significantly lower (P<0.05), in patients with high APP expression. Kasumi‑1 cells, which are A/E+, and the APP gene were used as the in vitro cell model to detect the mechanism of action in detail. Following the knockdown of APP expression, cell migration was significantly reduced (P<0.05). Furthermore, western blotting demonstrated that the protein expression of phosphorylated extracellular‑signal‑regulated kinase (p‑ERK), matrix metalloproteinase‑2 (MMP‑2) and c‑Myc was markedly reduced following interference of APP, while the expression of CXCR4 and MMP‑9 was not altered. Kasumi‑1 cells were co‑cultured with p‑ERK or c‑Myc inhibitors and demonstrated that the APP/p‑ERK/c‑Myc/MMP‑2 pathway was involved in signal transduction and regulation of cell migration. MicroRNA‑144 (miR‑144) mimics and transfected Kasumi‑1 cells were generated. Reverse transcription‑quantitative polymerase chain reaction and western blotting demonstrated that miR‑144 was a negative regulator of APP. Taken together, the findings of the present study suggest that miR‑144 negatively targets the APP gene and regulates cell migration via the APP/p‑ERK/c‑Myc/MMP‑2 pathway.
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August-2019
Volume 18 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Jiang L, Meng W, Yu G, Yin C, Wang Z, Liao L and Meng F: MicroRNA‑144 targets APP to regulate AML1/ETO+ leukemia cell migration via the p‑ERK/c‑Myc/MMP‑2 pathway. Oncol Lett 18: 2034-2042, 2019
APA
Jiang, L., Meng, W., Yu, G., Yin, C., Wang, Z., Liao, L., & Meng, F. (2019). MicroRNA‑144 targets APP to regulate AML1/ETO+ leukemia cell migration via the p‑ERK/c‑Myc/MMP‑2 pathway. Oncology Letters, 18, 2034-2042. https://doi.org/10.3892/ol.2019.10477
MLA
Jiang, L., Meng, W., Yu, G., Yin, C., Wang, Z., Liao, L., Meng, F."MicroRNA‑144 targets APP to regulate AML1/ETO+ leukemia cell migration via the p‑ERK/c‑Myc/MMP‑2 pathway". Oncology Letters 18.2 (2019): 2034-2042.
Chicago
Jiang, L., Meng, W., Yu, G., Yin, C., Wang, Z., Liao, L., Meng, F."MicroRNA‑144 targets APP to regulate AML1/ETO+ leukemia cell migration via the p‑ERK/c‑Myc/MMP‑2 pathway". Oncology Letters 18, no. 2 (2019): 2034-2042. https://doi.org/10.3892/ol.2019.10477