Down-regulation of circMUC16 inhibited the progression of ALL via interaction with miR-1182 and TPPP3.

Abstract

Circular RNA (circRNA) is crucial in various biological processes, particularly in the onset and progression of different diseases. Nevertheless, the function of circMUC16 in acute lymphoblastic leukemia (ALL) remains unclear. The expression of circMUC16, miR-1182 and TPPP3 was evaluated by qPCR. The role of circMUC16 in the progression of ALL was investigated bymcherry-EGFP-LC-3, cell cycle, flow cytometry apoptosis, caspase-3 activity, western blotting, and an in vivo xenograft model. The interactions among circMUC16, miR-1182, and TPPP3 were explored by using qPCR, western blot, dual-luciferase reporter, and RNA immunoprecipitation assays.In this study, it was found that circMUC16 was increased in ALL cells. Down-regulation of circMUC16 reduced autophagy, cell proliferation and increased apoptosis in vitro while inhibiting cancer in vivo. circMUC16 acted as a molecular sponge of miR-1182. The carcinogenic effect of circMUC16 was partially mediated by miR-409-3p. TPPP3 was shown to be a direct target of miR-1182 and to be competed with circMUC16. Overexpression of TPPP3 partially counteracted the inhibitory effects of sh-circMUC16 inhibition on malignant behaviors of ALL cells. This study revealed that the circMUC16/miR-1186/TPPP3 axis plays a crucial role in the progression of ALL, suggesting a novel therapeutic target for ALL therapy.