Upregulation of microRNA-126-5p is associated with drug resistance to cytarabine and poor prognosis in AML patients

Shibayama,Yoshihiko; Kondo,Takeshi; Ohya,Hiroki; Fujisawa,Shin-Ichi; Teshima,Takanori; Iseki,Ken

doi:10.3892/or.2015.3839

Upregulation of microRNA-126-5p is associated with drug resistance to cytarabine and poor prognosis in AML patients

Authors:
- Yoshihiko Shibayama
- Takeshi Kondo
- Hiroki Ohya
- Shin-Ichi Fujisawa
- Takanori Teshima
- Ken Iseki
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Affiliations: Education Research Center for Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan, Department of Hematology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan, Laboratory of Clinical Pharmaceutics and Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan, Department of Clinical Laboratory, Hokkaido University Hospital, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan
Published online on: March 6, 2015 https://doi.org/10.3892/or.2015.3839
Pages: 2176-2182
Copyright: © Shibayama et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

MicroRNAs (miRs) have been shown to negatively regulate gene expression by binding to mRNAs, and they play an important role in various physiological processes and malignancies. A previous study identified mature miR‑126-3p as an onco-microRNA that is generated from the pre‑microRNA, miR-126. Although miR-126 also generates mature miR‑126-5p, its function is less clear. In the present study, the relationship between miR-126-5p/3p expression levels and overall survival in 109 patients with acute myeloid leukemia (AML) who received intensive therapy were evaluated. Higher expression levels above the median value of miR-126-5p/3p were correlated with a poorer overall survival. The hazard ratio and 95% confidence intervals (95% CI) for the higher expression group relative to the lower expression group of miR-126-5p/3p were 2.098 (95% CI: 1.075-4.228) and 1.958 (95% CI: 1.001-3.927), respectively. An interaction was not observed between the hazard ratios of miR-126-5p and miR‑126-3p (p=0.73). Transfection of the mimic miR-126-5p into the AML cell line, KG-1, resulted in a decrease in the sensitivity to cytarabin and the expression level of Klotho mRNA as well as the elevation in the phosphorylation of Akt. The results of the present study demonstrated that higher expression levels of miR-126-5p/3p in patients with AML resulted in a poorer prognosis. Furthermore, miR-126-5p elevated the phosphorylation of Akt.

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