Hsa-miR-599 was identified as a tumor suppressor against cancer. This study aimed to explore possible mechanisms of antitumor effect of hsa-miR-599 against breast cancer. Tissue specimens were collected from 106 breast cancer cases, and breast cancer cell line MCF-7 was cultured for in vitro experiments. The expression pattern of hsa-miR-599 was measured via quantitative real-time polymerase chain reaction. Lipofectamine® 2000 reagent was used for cell transfection. Cell viability, motility and apoptosis were detected using MTT assay, transwell assay, and flow cytometer, respectively. Protein analysis was performed via western blot. Hsa-miR-599 expression was decreased in breast cancer tissues and cells. Moreover, its expression was negatively correlated with TNM stage (p = 0.004) and lymph node metastasis (p = 0.001). Enhanced hsa-miR-599 expression in breast cancer cells could induce the inhibition against cell proliferation, migration and invasion, and strengthen cell apoptosis. BRD4 might be a target of hsa-miR-599. Hsa-miR-599 combined with BRD4 inhibited breast cancer progression through targeting Jagged1/Notch1 pathway. Hsa-miR-599 expression is downregulated in breast cancer. Hsa-miR-599 may inactivate BRD4/Jagged1/Notch1 axis, thus suppressing malignant progression of breast cancer.

中文翻译：

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Hsa-miR-599 通过 BRD4/Jagged1/Notch1 轴抑制乳腺癌进展

Hsa-miR-599被鉴定为抗癌的肿瘤抑制因子。本研究旨在探讨hsa-miR-599对乳腺癌的抗肿瘤作用的可能机制。收集106例乳腺癌组织标本，培养乳腺癌细胞株MCF-7进行体外实验。通过定量实时聚合酶链反应测量hsa-miR-599的表达模式。Lipofectamine® 2000 试剂用于细胞转染。分别使用MTT法、transwell法和流式细胞仪检测细胞活力、运动性和凋亡。通过蛋白质印迹进行蛋白质分析。Hsa-miR-599在乳腺癌组织和细胞中表达降低。此外，其表达与TNM分期（p  = 0.004）和淋巴结转移（p  = 0.001）呈负相关。增强乳腺癌细胞中hsa-miR-599的表达可诱导抑制细胞增殖、迁移和侵袭，增强细胞凋亡。BRD4 可能是hsa-miR-599的靶标。Hsa-miR-599联合 BRD4 通过靶向 Jagged1/Notch1 通路抑制乳腺癌进展。Hsa-miR-599表达在乳腺癌中下调。Hsa-miR-599可能使BRD4/Jagged1/Notch1轴失活，从而抑制乳腺癌的恶性进展。