Department of Traumatic Orthopedics, The Second Affiliated Hospital, University of South China, Hengyang, China.
Department of Oncology, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou, China.
Cancer Biother Radiopharm. 2023 Nov;38(9):619-631. doi: 10.1089/cbr.2019.3349. Epub 2021 Mar 24.
Osteosarcoma (OS) is a common malignant bone cancer and usually occurs in adolescents and children. Circular RNAs (circRNAs) play essential roles in tumor development and progression. This study aimed to explore the function and molecular basis of circ_0016347 in OS progression. The levels of circ_0016347, miR-1225-3p, and ether à go-go 1 (KCNH1) were measured by quantitative real-time polymerase chain reaction or Western blot assay. Cell proliferation was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and colony formation assay. Cell migration and invasion were evaluated by transwell assay. Glucose consumption and lactate production were detected by glucose detection and lactic acid detection kits. The levels of Ki-67, matrix metalloproteinase-9 (MMP-9), and hexokinase-2 (HK2) were examined by Western blot assay. The interaction among circ_0016347, miR-1225-3p, and KCNH1 was validated by dual-luciferase reporter assay. Xenograft assay was conducted to analyze tumor growth . Circ_0016347 and KCNH1 were upregulated, while miR-1225-3p was downregulated in OS tissues or cells. Circ_0016347 and KCNH1 promoted proliferation, migration, invasion, and glycolysis of OS cells. Circ_0016347 regulated OS progression by modulating KCNH1. Circ_0016347 was a sponge of miR-1225-3p, and miR-1225-3p targeted KCNH1. Circ_0016347 regulated KCNH1 expression via sponging miR-1225-3p. Moreover, silencing of circ_0016347 inhibited tumor growth . Circ_0016347 contributed to OS progression through the miR-1225-3p/KCNH1 axis, which might provide a promising biomarker for OS therapy.
骨肉瘤(OS)是一种常见的恶性骨癌,通常发生在青少年和儿童中。环状 RNA(circRNA)在肿瘤的发生和发展中起着重要作用。本研究旨在探讨 circ_0016347 在 OS 进展中的作用和分子基础。通过实时定量聚合酶链反应或 Western blot 检测 circ_0016347、miR-1225-3p 和醚 á 去-go-go 1(KCNH1)的水平。通过 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐(MTT)测定法和集落形成测定法评估细胞增殖。通过 Transwell 测定法评估细胞迁移和侵袭。通过葡萄糖检测试剂盒和乳酸检测试剂盒检测葡萄糖消耗和乳酸生成。通过 Western blot 检测 Ki-67、基质金属蛋白酶-9(MMP-9)和己糖激酶-2(HK2)的水平。通过双荧光素酶报告基因检测验证 circ_0016347、miR-1225-3p 和 KCNH1 之间的相互作用。进行异种移植实验分析肿瘤生长情况。Circ_0016347 和 KCNH1 在 OS 组织或细胞中上调,而 miR-1225-3p 下调。Circ_0016347 和 KCNH1 促进 OS 细胞的增殖、迁移、侵袭和糖酵解。Circ_0016347 通过调节 KCNH1 来调节 OS 的进展。Circ_0016347 是 miR-1225-3p 的海绵,miR-1225-3p 靶向 KCNH1。Circ_0016347 通过海绵吸附 miR-1225-3p 来调节 KCNH1 的表达。此外,沉默 circ_0016347 抑制肿瘤生长。Circ_0016347 通过 miR-1225-3p/KCNH1 轴促进 OS 进展,这可能为 OS 治疗提供有前途的生物标志物。