title: Upregulation of microRNA-126-5p is associated with drug resistance to cytarabine and poor prognosis in AML patients.
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.
authors.affiliation: Education Research Center for Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Shibayama
authors.affiliation: Department of Hematology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Laboratory of Clinical Pharmaceutics and Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ohya
authors.affiliation: Department of Clinical Laboratory, Hokkaido University Hospital, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Fujisawa
authors.affiliation: Department of Hematology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Teshima
authors.affiliation: Laboratory of Clinical Pharmaceutics and Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D015153:Blotting, Western; D003561:Cytarabine / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D003561:Cytarabine