Circ_0000745 regulates NOTCH1-mediated cell proliferation and apoptosis in pediatric T-cell acute lymphoblastic leukemia through adsorbing miR-193b-3p

Abstract

ABSTRACT Background T-cell acute lymphoblastic leukemia (T-ALL) is a highly proliferative hematologic malignancy. Circular RNA hsa_circ_0000745 (circ_0000745) has been reported as an oncogene in acute lymphoblastic leukemia (ALL). However, whether circ_0000745 can drive T-ALL progression by controlling notch receptor 1 (NOTCH1) expression is unclear. Methods Relative expression of circ_0000745 and NOTCH1 in bone marrow (BM) samples and T-ALL cells was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Loss- and gain-of-function experiments were executed to evaluate the effects of circ_0000745 and NOTCH1 on T-ALL cell proliferation and apoptosis. The microRNAs (miRs) that might jointly interact with circ_0000745 and NOTCH1 were predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Results Circ_0000745 and NOTCH1 were overexpressed in T-ALL BM and T-ALL cells. Functionally, both circ_0000745 and NOTCH1 overexpression promoted T-ALL cell proliferation and curbed T-ALL cell apoptosis. In contrast, both circ_0000745 and NOTCH1 silencing restrained T-ALL cell proliferation and induced T-ALL cell apoptosis. Furthermore, circ_0000745 could control T-ALL cell proliferation and apoptosis through regulating NOTCH1 expression. Importantly, circ_0000745 regulated NOTCH1 expression by sponging miR-193b-3p. Conclusion Our findings proposed a novel model in which circ_0000745 promoted cell proliferation and curbed cell apoptosis via upregulating NOTCH1 through serving as a miR-193b-3p sponge in T-ALL.