Rapamycin inhibits the progression of human acute myeloid leukemia by regulating the circ_0094100/miR-217/ATP1B1 axis

Abstract

Rapamycin has been reported to inhibit the progression of diverse tumor cells. However, little is known about the functions of rapamycin in acute myeloid leukemia (AML). A Cell Counting Kit-8 (CCK-8) assay was conducted to evaluate cell viability. Flow cytometry analysis was employed to analyze cell apoptosis and cell cycle process. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to determine the levels of circRNA_0094100 (circ_0094100) and microRNA-217 (miR-217). Western blot assay was carried out to measure the protein levels of proliferating cell nuclear antigen (PCNA), cyclin D1, B-cell lymphoma-2 (Bcl-2) and ATPase Na+/K+ transporting subunit beta 1 (ATP1B1). Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were conducted to verify the relationship between miR-217 and circ_0094100 or ATP1B1. Rapamycin treatment suppressed AML cell viability and promoted apoptosis in a dose-dependent way. Circ_0094100 was elevated in AML tissues and cells. Moreover, the circ_0094100 level was reduced in AML cells treated with rapamycin. Circ_0094100 knockdown further inhibited rapamycin-mediated AML cell viability and cell cycle and promoted cell apoptosis. Circ_0094100 silencing reduced the protein levels of PCNA, cyclin D1, and Bcl-2 in rapamycin-treated AML cells. For mechanism analysis, circ_0094100 acted as the sponge for miR-217 and miR-217 inhibition reversed circ_0094100 knockdown-mediated malignant behaviors of rapamycin-treated AML cells. Furthermore, miR-217 overexpression suppressed cell viability and cell cycle and facilitated apoptosis in rapamycin-exposed AML cells, which were abolished by increasing ATP1B1. Rapamycin inhibited AML cell viability and cell cycle process and induced apoptosis through regulation of the circ_0094100/miR-217/ATP1B1 axis.