ABSTRACT

Osteosarcoma (OS) is a serious bone malignancy commonly occurred in childhood and adolescence. Circular RNA (circRNA) is a novel endogenous RNA that may be considered as a new biomarker for diseases’ diagnosis or prognosis. This study explored the roles and mechanism of circ_0001649 in OS. The qRT-PCR was performed to test circ_0001649 expression in OS tissues and cells. Luciferase was used to confirm the binding of circ_0001649 with miR-338-5p, miR-647 and miR-942. OS cells were stably transfected with pEX-circ_0001649 or miRNAs mimic, CCK-8 kit, colony formation, apoptosis and western blot analysis were used to detect the roles of circ_0001649. Circ_0001649 was low-expressed in OS tissues and cell lines. Circ_0001649 overexpression suppressed U2OS and HOS cell viability and survival fraction, and induced apoptosis presented as the increasing levels of Apaf-1, cleaved-caspase-3 and cleaved-caspase-9. Further, circ_0001649 worked as a sponge to absorb miR-338-5p, miR-647 and miR-942 to suppress cell proliferation, induce apoptosis and inhibit STAT pathway. Circ_0001649 suppressed OS cell proliferation and STAT pathway and induced apoptosis through sponging miR-338-5p, miR-647 and miR-942.

摘要

骨肉瘤（OS）是一种严重的骨恶性肿瘤，常见于儿童和青春期。环状RNA（circRNA）是一种新型内源性RNA，可被视为疾病诊断或预后的新生物标志物。本研究探讨了 circ_0001649 在 OS 中的作用和机制。进行 qRT-PCR 以测试 OS 组织和细胞中 circ_0001649 的表达。荧光素酶用于确认 circ_0001649 与 miR-338-5p、miR-647 和 miR-942 的结合。用pEX-circ_0001649或miRNAs模拟物稳定转染OS细胞，CCK-8试剂盒，集落形成、细胞凋亡和蛋白质印迹分析检测circ_0001649的作用。Circ_0001649 在 OS 组织和细胞系中低表达。Circ_0001649 过表达抑制了 U2OS 和 HOS 细胞活力和存活率，和诱导的细胞凋亡表现为 Apaf-1、cleaved-caspase-3 和 cleaved-caspase-9 水平的增加。此外，circ_0001649作为海绵吸收miR-338-5p、miR-647和miR-942以抑制细胞增殖、诱导细胞凋亡和抑制STAT通路。Circ_0001649 通过海绵 miR-338-5p、miR-647 和 miR-942 抑制 OS 细胞增殖和 STAT 通路并诱导细胞凋亡。