Shen Yuanyuan, Zhang Mengmeng, Da Liangshan, Huang Wei, Zhang Congjun
Department of Oncology, High-tech District of the First Affiliated Hospital of Anhui Medical University, No.120 Wan Shui Road, Hefei, Anhui, 230022, China.
Open Med (Wars). 2020 Sep 30;15(1):940-953. doi: 10.1515/med-2020-0223. eCollection 2020.
Breast cancer (BC) is the leading cause of cancer deaths in women worldwide. Circular RNA circ_SETD2 (circ_SETD2), also termed as hsa_circ_0065173, is reported to be abnormally expressed in BC. Nevertheless, the role and mechanism of circ_SETD2 in BC are unclear. Expression of circ_SETD2, miR-155-5p, and SCUBE2 mRNA was evaluated by quantitative real-time polymerase chain reaction. Cell cycle progression, proliferation, apoptosis, migration, and invasion were determined by flow cytometry, MTT, and transwell assays. The relationship between circ_SETD2 or SCUBE2 and miR-155-5p was verified through a dual-luciferase reporter assay. The role of circ_SETD2 in BC was confirmed by a xenograft assay. circ_SETD2 and SCUBE2 were downregulated, while miR-155-5p was upregulated in BC tissues and cells. Both circ_SETD2 and SCUBE2 elevation arrested cell cycle progression, inhibited cell proliferation, migration, and invasion, and accelerated cell apoptosis in BC cells. Moreover, circ_SETD2 upregulation repressed BC growth . Importantly, circ_SETD2 modulated SCUBE2 expression through competitively binding to miR-155-5p in BC cells. Also, the inhibitory impacts of circ_SETD2 enhancement on the malignant behavior of BC cells were restored by miR-155-5p overexpression. Besides, SCUBE2 silencing abolished miR-155-5p downregulation mediated effects on the malignant behavior of BC cells. Therefore, circ_SETD2 curbed BC progression via upregulating SCUBE2 via binding to miR-155-5p.
乳腺癌（BC）是全球女性癌症死亡的主要原因。环状RNA circ_SETD2（circ_SETD2），也称为hsa_circ_0065173，据报道在BC中异常表达。然而，circ_SETD2在BC中的作用和机制尚不清楚。通过定量实时聚合酶链反应评估circ_SETD2、miR-155-5p和SCUBE2 mRNA的表达。通过流式细胞术、MTT和Transwell实验确定细胞周期进程、增殖、凋亡、迁移和侵袭。通过双荧光素酶报告基因实验验证circ_SETD2或SCUBE2与miR-155-5p之间的关系。通过异种移植实验证实circ_SETD2在BC中的作用。在BC组织和细胞中，circ_SETD2和SCUBE2表达下调，而miR-155-5p表达上调。circ_SETD2和SCUBE2的升高均使BC细胞的细胞周期进程停滞，抑制细胞增殖、迁移和侵袭，并加速细胞凋亡。此外，circ_SETD2上调抑制BC生长。重要的是，在BC细胞中，circ_SETD2通过竞争性结合miR-155-5p调节SCUBE2的表达。此外，miR-155-5p过表达恢复了circ_SETD2增强对BC细胞恶性行为的抑制作用。此外，SCUBE2沉默消除了miR-155-5p下调介导的对BC细胞恶性行为的影响。因此，circ_SETD2通过与miR-155-5p结合上调SCUBE2来抑制BC进展。
