Abstract：
Circular RNAs (circRNAs) are key RNA molecules in cancer biology. CircRNA PR/SET domain 5 (circ_PRDM5, hsa_circ_0005654) was downregulated in breast cancer (BC) tissues. This study is designed to investigate the functional mechanism of circ_PRDM5 in BC. Ultrasound examinations were performed to evaluate BC patients and normal individuals. Circ_PRDM5, miR-25-3p, and Ankyrin repeat domain 46 (ANKRD46) level detection was carried out by reverse transcription-quantitative polymerase chain reaction. 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay was used for cell viability examination. Cell proliferation was evaluated by ethynyl-2\'-deoxyuridine assay and colony formation assay. The protein levels were examined using western blot. Cell migration and invasion abilities were assessed via transwell assay. Target interaction was analyzed via dual-luciferase reporter assay. The role of circ_PRDM5 in vivo was explored via xenograft tumor assay. Circ_PRDM5 expression was downregulated in BC tissues and cells. Overexpression of circ_PRDM5 suppressed proliferation and motility but enhanced apoptosis of BC cells. Circ_PRDM5 served as a sponge of miR-25-3p. Circ_PRDM5 impeded BC cell malignant development via sponging miR-25-3p. Circ_PRDM5 induced ANKRD46 upregulation by targeting miR-25-3p. Inhibition of miR-25-3p retarded BC progression by increasing the ANKRD46 level. Circ_PRDM5 repressed BC tumorigenesis in vivo through mediating the miR-25-3p/ANKRD46 axis. This study evidenced that circ_PRDM5 inhibited cell progression and tumor growth in BC via interacting with mir-25-3p/ANKRD46 network.
摘要：
环状RNA（circularRNAs）是癌症生物学中的关键RNA分子。circRNAPR/SET结构域5(circ_PRDM5,hsa_circ_0005654)在乳腺癌(BC)组织中下调。本研究旨在探讨circ_PRDM5在BC中的作用机制。进行超声检查以评估BC患者和正常人。Circ_PRDM5,miR-25-3p,通过逆转录-定量聚合酶链反应进行Ankyrin重复结构域46（ANKRD46）水平检测。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物(MTT)测定用于细胞活力检查。通过乙炔基-2'-脱氧尿苷测定和集落形成测定评估细胞增殖。使用蛋白质印迹检查蛋白质水平。通过transwell测定评估细胞迁移和侵袭能力。通过双荧光素酶报告基因测定分析靶标相互作用。通过异种移植肿瘤试验探讨了circ_PRDM5在体内的作用。Circ_PRDM5表达在BC组织和细胞中下调。circ_PRDM5的过表达抑制了BC细胞的增殖和运动，但增加了BC细胞的凋亡。Circ_PRDM5充当miR-25-3p的海绵。Circ_PRDM5通过海绵作用miR-25-3p阻碍BC细胞恶性发展。Circ_PRDM5通过靶向miR-25-3p诱导ANKRD46上调。miR-25-3p的抑制通过增加ANKRD46水平来延缓BC进展。Circ_PRDM5通过介导miR-25-3p/ANKRD46轴在体内抑制BC肿瘤发生。这项研究证明circ_PRDM5通过与mir-25-3p/ANKRD46网络相互作用抑制BC中的细胞进展和肿瘤生长。
