Upregulation of miR-96-5p Expression Inhibits Malignant Progression in T-cell Acute Lymphoblastic Leukemia by Targeting Spleen Tyrosine Kinase

Abstract

Background: Although advances in treatment have increased the five-year overall survival of pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL) to >80%, relapse, resulting in poor prognosis, remains a considerable challenge for all age groups. Therefore, further improvements in T-ALL treatment are required. This study aimed to determine the roles of miR-96-5p and spleen tyrosine kinase (SYK) as novel therapeutic targets that regulate T-ALL cells. Methods: The expression levels of miR-96-5p and SYK were evaluated from patient samples, and the correlation between the two was determined. The effects of miR-96-5p on the proliferation of T-ALL cells were detected using the cell counting kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assays. The effect of miR-96-5p on T-ALL cell apoptosis was evaluated by flow cytometry. In addition, bioinformatics analysis, luciferase reporter assays, and rescue assays were used to verify whether SYK was a downstream target of miR-96-5p. The regulatory relationship between miR-96-5p and SYK was also analyzed. Results: The results showed that the expression of miR-96-5p was lower in patients with T-ALL than in healthy volunteers (p < 0.05). Additionally, miR-96-5p enhanced proliferation and inhibited apoptosis of T-ALL cells in vitro. Furthermore, the expression of SYK and miR-96-5p in T-ALL patients showed an opposite trend, and this negative correlation was also reflected in the effect on cells. Conclusions: This study demonstrated that miR-96-5p and SYK may be potential therapeutic targets for regulating T-ALL cell proliferation and apoptosis at the cellular level.