Department Orthopedics, Huai'an Second People's Hospital, Huai'an City, JiangSu Province, China.
Department Orthopedics, Huaian Hospital Affiliated to Xuzhou Medical University, Huai'an City, Jiangsu, China.
Bioengineered. 2022 Mar;13(3):7351-7366. doi: 10.1080/21655979.2022.2037869.
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 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 . In conclusion, Circ_ANKIB1 binds miR-26b-5p and modulates EZH2 to accelerate the chemo-resistance of osteosarcoma.
骨肉瘤是儿童和青少年中常见的骨恶性肿瘤。化疗药物耐药性是影响骨肉瘤患者手术效果和预后的主要因素。本研究评估了环状 RNA _ANKIB1 在骨肉瘤发生发展中的作用和机制。通过 RT-qPCR 检测 OS 样本中环状 RNA(circ)_ANKIB1、微小 RNA(miR)-26b-5p、增强子的组蛋白 H2A 家族成员 EZH2 的表达。通过 Western blot 分析多药耐药蛋白 1(MRP1)、P-糖蛋白(P-gp)和脂蛋白受体相关蛋白(LRP)的蛋白表达。评估 circ_ANKIB1 与骨肉瘤患者临床病理特征发生的相关性;分析 circ_ANKIB1 的环状特征。使用 hFOB1.19、KHOS、U2-OS 骨肉瘤细胞研究多柔比星(Doxorubicin,DXR)耐药细胞的半抑制浓度 IC50、克隆形成、侵袭和凋亡。通过荧光素酶报告基因实验研究 circ_ANKIB1 与 miR-26b-5p 的结合以及 miR-26b-5p 与 EZH2 的靶向作用。进行了皮下致瘤实验。沉默骨肉瘤组织和细胞及 DXR 耐药骨肉瘤组织和细胞中的 miR-26b-5p,同时上调 circ_ANKIB1 和 EZH2。沉默 circ_ANKIB1 上调 miR-26b-5p,抑制 EZH2、MRP1、P-gp、LRP、IC50,并促进骨肉瘤进展。Circ_ANKIB1 与 miR-26b-5p 结合。降低 miR-26b-5p 逆转了沉默 circ_ANKIB1 对 DXR 耐药 OS 细胞的影响。miR-26b-5p 靶向 EZH2,上调 miR-26b-5p 逆转了增加 miR-26b-5p 对 DXR 耐药细胞的影响。沉默 circ_ANKIB1 抑制了裸鼠体内的 DXR 耐药骨肉瘤细胞。总之,Circ_ANKIB1 结合 miR-26b-5p 并调节 EZH2 以加速骨肉瘤的化疗耐药性。