Oncology Research, Pfizer Worldwide Research and Development, San Diego, California, United States of America.
PLoS One. 2013 Apr 24;8(4):e62170. doi: 10.1371/journal.pone.0062170. Print 2013.
Patients with triple-negative breast cancers (TNBCs) typically have a poor prognosis. TNBCs are characterized by their resistance to apoptosis, aggressive cellular proliferation, migration and invasion, and currently lack molecular markers and effective targeted therapy. Recently, miR-221/miR-222 have been shown to regulate ERα expression and ERα-mediated signaling in luminal breast cancer cells, and also to promote EMT in TNBCs. In this study, we characterized the role of miR-221 in a panel of TNBCs as compared to other breast cancer types. miR-221 knockdown not only blocked cell cycle progression, induced cell apoptosis, and inhibited cell proliferation in-vitro but it also inhibited in-vivo tumor growth by targeting p27(kip1). Furthermore, miR-221 knockdown inhibited cell migration and invasion by altering E-cadherin expression, and its regulatory transcription factors Snail and Slug in human TNBC cell lines. Therefore, miR-221 functions as an oncogene and is essential in regulating tumorigenesis in TNBCs both in vitro as well as in vivo.
三阴性乳腺癌（TNBC）患者通常预后不良。TNBC 的特征是对细胞凋亡、侵袭、迁移和增殖具有抵抗性，目前缺乏分子标志物和有效的靶向治疗方法。最近，miR-221/miR-222 被证明可以调节腔乳腺癌细胞中 ERα 的表达和 ERα 介导的信号转导，也可以促进 TNBC 中的 EMT。在这项研究中，我们比较了 TNBC 与其他乳腺癌类型的 panel 来研究 miR-221 的作用。miR-221 敲低不仅在体外阻断细胞周期进程、诱导细胞凋亡和抑制细胞增殖，而且通过靶向 p27(kip1) 抑制体内肿瘤生长。此外，miR-221 敲低通过改变 E-钙黏蛋白表达及其调节转录因子 Snail 和 Slug 抑制人 TNBC 细胞系中的细胞迁移和侵袭。因此，miR-221 作为癌基因发挥作用，在调节 TNBC 的体外和体内肿瘤发生中是必不可少的。
