Shibayama Yoshihiko, Kondo Takeshi, Ohya Hiroki, Fujisawa Shin-Ichi, Teshima Takanori, Iseki Ken
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.
Oncol Rep. 2015 May;33(5):2176-82. doi: 10.3892/or.2015.3839. Epub 2015 Mar 6.
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.
微小RNA(miRs)已被证明可通过与信使核糖核酸(mRNAs)结合来负向调节基因表达,并且它们在各种生理过程和恶性肿瘤中发挥重要作用。先前的一项研究确定成熟的miR-126-3p是一种源自前体微小RNA(pre-miR-126)的致癌微小RNA。虽然miR-126也产生成熟的miR-126-5p,但其功能尚不清楚。在本研究中,评估了109例接受强化治疗的急性髓系白血病(AML)患者中miR-126-5p/3p表达水平与总生存期之间的关系。高于miR-126-5p/3p中位数的较高表达水平与较差的总生存期相关。miR-126-5p/3p高表达组相对于低表达组的风险比和95%置信区间(95%CI)分别为2.098(95%CI:1.075 - 4.228)和1.958(95%CI:1.001 - 3.927)。未观察到miR-126-5p和miR-126-3p风险比之间的相互作用(p = 0.73)。将模拟miR-126-5p转染到AML细胞系KG-1中,导致对阿糖胞苷的敏感性降低、Klotho信使核糖核酸表达水平降低以及Akt磷酸化水平升高。本研究结果表明,AML患者中miR-126-5p/3p的较高表达水平导致预后较差。此外,miR-126-5p升高了Akt的磷酸化水平。