Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China.
Thorac Cancer. 2023 Jun;14(18):1707-1718. doi: 10.1111/1759-7714.14916. Epub 2023 May 2.
Growing evidence has revealed the critical regulatory role for circular RNAs (circRNAs) in cancer. This study aimed to explore the function of circ_0001387 in breast cancer (BC).
Circ_0001387, miR-136-5p, and spindle and kinetochore-associated protein 2 (SKA2) levels were analyzed by quantitative real-time polymerase chain reaction. Clone formation and 5-ethynyl-2'-deoxyuridine assays were used to analyze cell proliferation. Cell apoptosis and cell migration and invasion abilities were analyzed using flow cytometry or transwell assay. Mechanism assay was used to confirm the association between miR-136-5p and circ_0001387 or SKA2. The effect of circ_0001387 on tumor growth in vivo was analyzed by the xenograft mice model.
Circ_0001387 and SKA2 were expressed at high levels, whereas miR-136-5p was lowly expressed in BC tissues and cells. Meanwhile, the downregulation of circ_0001387 restrained BC cell progression in vitro and in vivo. Circ_0001387 competitively bound to miR-136-5p to regulate BC cell malignant behaviors. SKA2 was targeted by miR-136-5p, and SKA2 reinstated the suppressive effect of miR-136-5p upregulation in BC cells.
Our study indicated that circ_0001387 contributed to BC cell progression through miR-136-5p/SKA2 axis.
越来越多的证据表明环状 RNA（circRNAs）在癌症中具有关键的调控作用。本研究旨在探讨 circ_0001387 在乳腺癌（BC）中的功能。
采用实时定量聚合酶链反应分析 circ_0001387、miR-136-5p 和纺锤体和着丝粒相关蛋白 2（SKA2）的水平。克隆形成和 5-乙炔基-2'-脱氧尿苷实验用于分析细胞增殖。流式细胞术或 Transwell 实验用于分析细胞凋亡和细胞迁移及侵袭能力。机制实验用于验证 miR-136-5p 与 circ_0001387 或 SKA2 之间的关联。通过异种移植小鼠模型分析 circ_0001387 对体内肿瘤生长的影响。
circ_0001387 和 SKA2 在 BC 组织和细胞中表达水平较高，而 miR-136-5p 表达水平较低。同时，circ_0001387 的下调抑制了 BC 细胞的体外和体内进展。circ_0001387 竞争性结合 miR-136-5p 调节 BC 细胞恶性行为。SKA2 是 miR-136-5p 的靶标，SKA2 恢复了 miR-136-5p 上调对 BC 细胞的抑制作用。
本研究表明，circ_0001387 通过 miR-136-5p/SKA2 轴促进 BC 细胞进展。
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