The First Department of Breast Cancer, Tianjin Medical University Cancer Institute Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Thorac Cancer. 2020 Nov;11(11):3181-3192. doi: 10.1111/1759-7714.13641. Epub 2020 Oct 1.
Breast cancer (BC) is a heterogeneous malignant tumor that threatens the health of women worldwide. Hsa_circRNA_0000518 (circ_0000518) has been revealed to be upregulated in BC tissues. However, the role and mechanism of circ_0000518 in BC are indistinct.
Quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to detect the levels of circ_0000518, microRNA (miR)-326, and fibroblast growth factor receptor 1 (FGFR1) mRNA in BC tissues and cells. Cell counting kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays were executed to estimate BC cell proliferation, cell cycle progression, apoptosis, migration, and invasion. The relationship between circ_0000518 or FGFR1 and miR-326 was verified by dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. The role of circ_0000518 in vivo was confirmed by xenograft assay.
Circ_0000518 and FGFR1 were upregulated while miR-326 was downregulated in BC tissues and cells. Circ_0000518 silencing impeded tumor growth in vivo and induced cell cycle arrest, apoptosis, cured proliferation, colony formation, migration, and invasion of BC cells in vitro. Circ_0000518 regulated FGFR1 expression via competitively binding to miR-326 in BC cells. MiR-326 inhibitor reversed the inhibitory influence of circ_0000518 knockdown on the malignant behaviors of BC cells. FGFR1 overexpression abolished miR-326 mimic-mediated influence on the malignant behaviors of BC cells.
Circ_0000518 facilitated BC development via regulation of the miR-326/FGFR1 axis, suggesting that circ_0000518 might be a promising target for BC treatment.
乳腺癌（BC）是一种威胁全球女性健康的异质性恶性肿瘤。已经发现 hsa_circRNA_0000518（circ_0000518）在 BC 组织中上调。然而，circ_0000518 在 BC 中的作用和机制尚不清楚。
采用实时定量聚合酶链反应（qRT-PCR）检测 BC 组织和细胞中 circ_0000518、microRNA（miR）-326 和成纤维细胞生长因子受体 1（FGFR1）mRNA 的水平。采用细胞计数试剂盒-8（CCK-8）、集落形成、流式细胞术和 Transwell 测定法评估 BC 细胞增殖、细胞周期进程、细胞凋亡、迁移和侵袭。通过双荧光素酶报告和/或 RNA 免疫沉淀（RIP）测定验证 circ_0000518 或 FGFR1 与 miR-326 的关系。通过异种移植实验证实 circ_0000518 在体内的作用。
BC 组织和细胞中 circ_0000518 和 FGFR1 上调，miR-326 下调。circ_0000518 沉默抑制体内肿瘤生长，并诱导 BC 细胞体外细胞周期停滞、凋亡、增殖抑制、集落形成、迁移和侵袭。circ_0000518 通过与 BC 细胞中的 miR-326 竞争结合来调节 FGFR1 的表达。miR-326 抑制剂逆转了 circ_0000518 敲低对 BC 细胞恶性行为的抑制作用。FGFR1 过表达消除了 miR-326 模拟对 BC 细胞恶性行为的影响。
circ_0000518 通过调节 miR-326/FGFR1 轴促进 BC 的发展，表明 circ_0000518 可能是 BC 治疗的一个有前途的靶点。
