Circular RNA_ANKIB1 accelerates chemo-resistance of osteosarcoma via binding microRNA-26b-5p and modulating enhancer of zeste homolog 2

ABSTRACT

Osteosarcoma is a common bone malignancy in children and adolescents. Chemotherapeutic drug resistance is the major factor impacting the surgical outcome and prognosis of patients with osteosarcoma. This investigation assessed the role and mechanism of circular RNA_ANKIB1 in the development of osteosarcoma. The circular RNA (circ) _ANKIB1, microRNA (miR)-26b-5p, enhancer of zeste homolog 2 (EZH2) expression in OS samples was investigated through RT-qPCR. The EZH2, multidrug resistance protein 1 (MRP1), P-gp, and lipoprotein receptor-related protein (LRP) protein expressions were analyzed through western blot. The association between circ_ANKIB1 and the occurrence of clinic-pathological features in OS patients was assessed; the circular features of circ_ANKIB1 were analyzed. The hFOB1.19, KHOS, U2-OS OS cells were used to study the semi-inhibitory concentration IC50 of Doxorubicin (DXR)-resistant cells, clone formation, invasion, and apoptosis. The luciferase assay was used to study the binding of circ-ANKIB1 with miR-26b-5p and the targeting of miR-26b-5p with EZH2. In vivo experiments were performed via subcutaneous tumorigenic experiments. MiR-26b-5p in OS tissues and cells and DXR-resistant OS tissues and cells was silenced while circ_ANKIB1 and EZH2 were elevated. Circ_ANKIB1 silencing elevated miR-26b-5p, repressed EZH2, MRP1, P-gp, LRP, IC50, and elevated OS advancement. Circ_ANKIB1 bind miR-26b-5p. Reduced miR-26b-5p revered the influence of silencing circ_ANKIB1 on DXR resistant OS cells. MiR-26b-5p targeted EZH2, and EZH2 elevation reversed the impact of increasing miR-26b-5p on DXR resistant cells. Circ_ANKIB1 silencing suppressed DXR-resistant OS cells in vivo. In conclusion, Circ_ANKIB1 binds miR-26b-5p and modulates EZH2 to accelerate the chemo-resistance of osteosarcoma.

Graphical abstract