■微RNA(miRNA)作为肿瘤抑制因子或癌基因,被称为oncomiRs,是癌症靶向治疗的一个有希望的新焦点。大约16%的乳腺癌患者患有糖尿病。乳腺癌伴2型糖尿病(BDM)具有其独特的生物学特性和临床特点。这项研究主要调查了miR-29a在BDM患者中的治疗潜力和调节机制。
■通过乳腺组织中的实时逆转录酶聚合酶链反应(qRT-PCR)分析了BDM中miR-29a的重要性。通过使用在高水平的葡萄糖和胰岛素培养的3T3-L1脂肪细胞中培养的MDA-MB-231细胞来建立BDM的细胞模型。通过高脂饮食加低剂量链脲佐菌素(STZ)在雌性BALB/c小鼠中诱导2型糖尿病(T2DM)小鼠模型。通过使用MDA-MB-231细胞在这些T2DM小鼠上建立用于BDM的异种移植小鼠模型。然后研究慢病毒-shRNAs介导的miR-29a敲低对细胞增殖的生物学效应,凋亡,细胞周期,和迁移进行了调查。
■我们的结果表明miR-29a在BDM患者中上调,这与预后较差有关。在人类乳腺癌细胞中,miR-29a敲低降低了BDM中的细胞增殖以及细胞迁移和侵袭。在T2DM异种移植物中,miR-29a敲低抑制MDA-MB-231细胞肿瘤发生和转移。我们还证明miR-29a通过靶向Sirtuin1(SIRT1)促进BDM细胞生长和转移。
■我们的发现表明,抗miR-29a通过靶向SIRT1抑制BDM中的细胞增殖和侵袭。我们相信抗miR-29a可能代表了BDM患者的一种新的治疗方法。
UNASSIGNED: MicroRNAs (miRNAs) acting as tumour suppressors or oncogenes, known as oncomiRs, are a promising new focus in targeted therapies for cancer. Approximately 16% of breast cancer patients have pre-existing diabetes. Breast cancer with type 2 diabetes mellitus (BDM) is provided with its unique biological characteristics and clinical characteristics. This
study primarily investigated the therapeutic potential and regulatory mechanism of miR-29a in patients with BDM.
UNASSIGNED: The significance of miR-29a in BDM was analyzed by real-time reverse transcriptase polymerase chain reaction (qRT-PCR) in breast tissues. A cell model for BDM was established by using MDA-MB-231 cells cultured in 3T3-L1 adipocytes cultured with high levels of glucose and insulin. A type 2 diabetes mellitus (T2DM) mouse model was induced in female BALB/c mice through a high-fat diet plus low doses of streptozotocin (STZ). The xenograft mouse-model for BDM was established on these T2DM mouse by using MDA-MB-231 cells. Then the biological effects of miR-29a knockdown mediated by lentivirus-shRNAs on cell proliferation, apoptosis, cell cycle, and migration were investigated.
UNASSIGNED: Our results indicated that miR-29a was upregulated in patients with BDM, which correlated with a worse prognosis. In human breast cancer cells, miR-29a knockdown reduced cell proliferation and cell migration and invasion in BDM. In the T2DM xenograft, miR-29a knockdown suppressed MDA-MB-231 cells tumorigenesis and metastasis. We also demonstrated that miR-29a promoted BDM cell growth and metastasis by targeting Sirtuin 1 (SIRT1).
UNASSIGNED: Our findings indicated that anti-miR-29a inhibited cell proliferation and invasion in BDM by targeting SIRT1. We believe anti-miR-29a may represent a novel therapeutic approach for the management of patients with BDM.