Breast Cancer Center, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital.
Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University.
Yakugaku Zasshi. 2021 Mar 1;141(3):415-426. doi: 10.1248/yakushi.20-00160. Epub 2020 Oct 28.
Doxorubicin (DOX) is currently one of the most widely used and effective drugs for the treatment of breast cancer, but drug resistance in breast cancer often leads to poor efficacy. MicroRNAs (miRNAs) are involved in the development and progression of various tumors and increasing number of studies have confirmed that abnormal miR-520b expression is closely associated breast cancer. We analyzed the clinical features, including miR-520b, of 30 patients with breast cancer. Further, we analyzed the interaction between miR-520b and insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cell. miR-520b expression was significantly increased in chemotherapy-sensitive patients and was positively correlated with the chemotherapeutic efficacy in breast cancer. Cell proliferation assay confirmed that miR-520b promotes DOX-induced breast cancer cell apoptosis by regulating the PI3K/AKT signaling pathway. Moreover, bioinformatics method and dual luciferase reporter assay demonstrated that miR-520b negatively regulates IGF-1R, and IGF-1R overexpression and enhanced activity are closely associated with tumor development, progression, metastasis, and chemotherapy resistance. Similarly, cell proliferation assay showed that IGF-1R is negatively correlated with the efficacy of DOX chemotherapy and affects cell apoptosis mediated by the PI3K/AKT signaling pathway. On the contrary, miR-520b can downregulate the expression of IGF-1R. miR-520b increases DOX sensitivity and promotes cell apoptosis in breast cancer by inhibiting IGF-1R expression by the PI3K/AKT signaling pathway.
阿霉素（DOX）是目前最广泛使用和有效的乳腺癌治疗药物之一，但乳腺癌的耐药性常常导致疗效不佳。microRNAs（miRNAs）参与各种肿瘤的发生和发展，越来越多的研究证实异常miR-520b 表达与乳腺癌密切相关。我们分析了 30 例乳腺癌患者的临床特征，包括 miR-520b。进一步分析了 miR-520b 与胰岛素样生长因子 1 受体（IGF-1R）在乳腺癌细胞中的相互作用。miR-520b 在化疗敏感患者中的表达显著增加，并与乳腺癌的化疗疗效呈正相关。细胞增殖实验证实，miR-520b 通过调节 PI3K/AKT 信号通路促进 DOX 诱导的乳腺癌细胞凋亡。此外，生物信息学方法和双荧光素酶报告基因实验表明，miR-520b 负调控 IGF-1R，IGF-1R 的过表达和活性增强与肿瘤的发生、发展、转移和化疗耐药密切相关。同样，细胞增殖实验表明 IGF-1R 与 DOX 化疗疗效呈负相关，并影响 PI3K/AKT 信号通路介导的细胞凋亡。相反，miR-520b 可以下调 IGF-1R 的表达。miR-520b 通过 PI3K/AKT 信号通路抑制 IGF-1R 表达，增加 DOX 敏感性，促进乳腺癌细胞凋亡。
