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

H.-X. Qi, Q. Cao, X.-Z. Sun, W. Zhou, Z. Hong, J. Hu, C.-X Juan, S. Li, W.-X. Kuai

Department Of Pediatrcis, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, China. kwx9743@163.com

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• Hematology

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.

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