MiR-410 regulates malignant biological behavior of pediatric acute lymphoblastic leukemia through targeting FKBP5 and Akt signaling pathway

Eur Rev Med Pharmacol Sci. 2018 Dec;22(24):8797-8804. doi: 10.26355/eurrev_201812_16647.

Abstract

Objective: The aim of this study was to investigate the role of miR-410 in regulating the proliferation and apoptosis of pediatric acute lymphoblastic leukemia (ALL) cells and to explore the possible underlying mechanism.

Patients and methods: The expression level of miR-410 in ALL cases and cells was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Luciferase reporter gene assay was performed to evaluate the interaction between miR-410 and FKBP5. MTT and colony formation assay were used to determine the effect of miR-410 on the proliferation and colony formation ability of ALL cells. The effect of miR-410 on cell apoptosis was measured by Annexin V-fluorescein isothiocyanate 1 (FITC) and propidium iodide (PI). Western blot was used to analyze the effect of miR-410 on the protein expression levels of phosphorylated Akt (p-Akt) and cleaved caspase-3.

Results: In our investigation, miR-410 was significantly up-regulated in ALL cases and cells. We searched three public databases to predict the potential target of miR-410, and found that FKBP5 was a direct target of miR-410. Meanwhile, Luciferase reporter gene assay confirmed our hypothesis. The overexpression of miR-410 accelerated the proliferation and colony formation ability of ALL cells, whereas remarkably decreased cell apoptosis rate. Western blotting showed that miR-410 inhibited the activation of Akt signaling pathway. However, FKBP5 could reverse the effects of miR-410.

Conclusions: MiR-410 regulated the proliferation, colony formation and apoptosis of ALL cells through targeting FKBP5 and Akt signal pathway, indicating that miR-410 might be a potential therapeutic target for the treatment of ALL.

MeSH terms

  • Adolescent
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Infant
  • Male
  • MicroRNAs / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / genetics*
  • Tacrolimus Binding Proteins / genetics*
  • Up-Regulation

Substances

  • MIRN410 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-akt
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5