MiR-598-3p functions as a tumor suppressor in pediatric T-cell acute lymphoblastic leukemia

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.