circ-KEL在急性髓系白血病中的表达及其对白血病细胞的调控作用和机制

OBJECTIVE: To explore the expression of circ-KEL in patients with acute myeloid leukemia (AML) and the effect and mechanism of circ-KEL on leukemic cells. METHODS: The expression of circ-KEL was detected by quantitative real-time polymerase chain reaction in bone marrow mononuclear cells collected from 116 patients with AML and 40 healthy donors. The correlation of circ-KEL expression with the clinical characteristics of patients with AML was further systematically analyzed. The modulations among circ-KEL, miR-335-5p, and LRG1 were predicted through bioinformatics analysis and validated by dual luciferase assay. Cell proliferation and apoptosis were detected using CCK8 and flow cytometry. RESULTS: The expression of circ-KEL was significantly elevated in patients with AML compared with the healthy controls（Relative expression level, −Δct, AML: −7.117±1.831; control: −8.669±1.771, P<0.001）. Moreover, patients with high circ-KEL expression have significantly worse overall survival. The level of circ-KEL in patients with AML was downregulated after chemo-treatment. In addition, circ-KEL could serve as the sponge of miR-335-5p and regulate LRG1. Bioinformatics analysis showed that miR-335-5p correlates with good prognosis and was negatively associated with LRG1. LRG1 could promote cell proliferation and inhibit cell apoptosis. Our results also exhibited the higher expression of LRG1 in patients with AML. Moreover, circ-KEL exerted functional effects via sponging miR-335-5p and regulating LRG1. CONCLUSION: circ-KEL expresses highly in patients with AML and correlates with poor prognosis, suggesting its important role in the genesis and progress of AML.