Abstract

 
 
 
 Purpose: To investigate the role of miR-598-3p in pediatric T-cell acute lymphoblastic leukemia (T- ALL).
 Methods: The expression of miR-598-3p in mononuclear cells isolated from the peripheral blood samples of children with or without T-ALL was assessed using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cell viability or proliferation of T-ALL cell lines was evaluated using cell counting kit-8 assay or bromodeoxyuridine staining, respectively. The target gene of miR-598-3p was predicted and validated using luciferase reporter assay, while the underlying mechanism involved in miR-598-3p-mediated T-ALL was determined by western blot analysis.
 Results: MiR-598-3p was reduced in the peripheral blood mononuclear cells of T-ALL patients. Ectopic miR-598-3p expression decreased T-ALL cell viability and suppressed proliferation, while miR-598-3p interference showed reversed effects. Additionally, the target gene of miR-598-3p, Dishevelled, EGL-10, and Pleckstrin domain-containing mTOR-interacting protein (DEPTOR), was down-regulated by miR- 598-3p in T-ALL. MiR-598-3p decreased phospho (p)-AKT protein expression, while AKT inhibition counteracted the suppressive effects of miR-598-3p silencing on T-ALL cell viability and proliferation.
 Conclusion: MiR-598-3p/DEPTOR is involved in the proliferation of T-ALL through AKT pathway, thus providing a potential novel application in pediatric T-ALL.
 
 
 
Highlights
Acute lymphoblastic leukemia (ALL), the most common hematologic tumor in children, accounts for approximately 25 % of pediatric cancers [1]
A significant decrease in miR-598-3p was observed in samples from pediatric T-cell ALL (T-ALL) compared with those from healthy children (p < 0.01) (Figure 1), suggesting that miR-598-3p might be involved in T-ALL progression
Analysis of the clinical and immunophenotypic features between pediatric T-ALL patients and healthy children suggested that the hemoglobin level, white blood cell count, and platelet count showed significant differences (Table 2)
Summary
Acute lymphoblastic leukemia (ALL), the most common hematologic tumor in children, accounts for approximately 25 % of pediatric cancers [1]. T-ALL cells were transfected with miR-598-3p mimic, inhibitor and the corresponding negative controls (NC mimic, NC inhibitor) (GenePharma, Shanghai, China) using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s instructions. The miR-598-3p expression levels in the peripheral blood mononuclear cells of pediatric T-ALL patients were examined, and the role and mechanism of miR-598-3p in T-ALL were investigated. The cells were incubated with 20 μL of cell counting kit-8 solution for 4 h before measuring the absorbance at 450 nm using the Epoch microplate Reader (BioTek, Winooski, VT, USA) according to manufacturer’s instructions. The cells were incubated with 10 μL of 10 mM bromodeoxyuridine for 2 h before measuring the absorbance at 450 nm according to the manufacturer’s instructions. SPSS 17.0. p < 0.05 was considered statistically significant
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