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Article

MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS

  • Authors:
    • Yi Xiao
    • Taoran Deng
    • Changliang Su
    • Zhen Shang
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
  • Pages: 4986-4994
    |
    Published online on: April 24, 2017
       https://doi.org/10.3892/ol.2017.6076
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Abstract

Acute myeloid leukemia (AML) is a heterogeneous malignant disorder derived from the myeloid hematopoietic cells that accounts for ~80% of all adult acute leukemia. Numerous studies have shown that drug resistance not only exists against conventional chemotherapeutic drugs, but also limits the efficacy of new biological agents. Therefore, it is important to identify the mechanisms behind chemoresistance and seek therapeutic strategies to enhance efficacy in AML chemotherapy. MicroRNA (miR)‑217 has been recognized as a tumor suppressor that is downregulated in various types of cancer, however the mechanisms behind the expression and function of miR‑217 in AML have not yet been recognized. The expression of miR‑217 was determined by quantitative polymerase chain reaction (qPCR). Following transfection with miR‑217 mimics, an MTT assay, chemosensitivity assay, cell apoptosis assay and western blot analysis were performed in AML cell lines. Functional assays were also performed to explore the effects of endogenous Kirsten rat sarcoma viral oncogene homolog (KRAS) in AML. The results revealed that miR‑217 was downregulated in patients with AML. Overexpression of miR‑217 inhibited cellular proliferation and enhanced cell chemosensitivity to doxorubicin by the cell apoptosis pathway in AML cells. A dual‑luciferase reporter assay demonstrated that KRAS was a direct target gene of miR‑217 in vitro. qPCR and western blot analysis revealed that miR‑217 negatively regulated KRAS protein expression, but had no impact on KRAS mRNA expression. Knockdown of KRAS expression markedly suppressed AML cellular proliferation, and enhanced cell chemosensitivity to doxorubicin via the cell apoptosis pathway. These findings indicate that miR‑217 functions as a tumor suppressor in AML by directly targeting KRAS. Therefore, miR‑217‑based therapeutic strategies may provide a novel strategy for the enhancement of efficacy in the treatment of AML.
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Copy and paste a formatted citation
Spandidos Publications style
Xiao Y, Deng T, Su C and Shang Z: MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS. Oncol Lett 13: 4986-4994, 2017.
APA
Xiao, Y., Deng, T., Su, C., & Shang, Z. (2017). MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS. Oncology Letters, 13, 4986-4994. https://doi.org/10.3892/ol.2017.6076
MLA
Xiao, Y., Deng, T., Su, C., Shang, Z."MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS". Oncology Letters 13.6 (2017): 4986-4994.
Chicago
Xiao, Y., Deng, T., Su, C., Shang, Z."MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS". Oncology Letters 13, no. 6 (2017): 4986-4994. https://doi.org/10.3892/ol.2017.6076
Copy and paste a formatted citation
x
Spandidos Publications style
Xiao Y, Deng T, Su C and Shang Z: MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS. Oncol Lett 13: 4986-4994, 2017.
APA
Xiao, Y., Deng, T., Su, C., & Shang, Z. (2017). MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS. Oncology Letters, 13, 4986-4994. https://doi.org/10.3892/ol.2017.6076
MLA
Xiao, Y., Deng, T., Su, C., Shang, Z."MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS". Oncology Letters 13.6 (2017): 4986-4994.
Chicago
Xiao, Y., Deng, T., Su, C., Shang, Z."MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS". Oncology Letters 13, no. 6 (2017): 4986-4994. https://doi.org/10.3892/ol.2017.6076
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