Department of Radiation Oncology, Nan Fang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Department of Radiation Oncology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, Guangdong 511500, P.R. China.
Oncol Rep. 2018 Jun;39(6):2635-2643. doi: 10.3892/or.2018.6379. Epub 2018 Apr 18.
Triple‑negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that lacks effective targeted therapies. In the present study, we revealed that the expression of miR‑30a was significantly decreased in TNBC, and TNBC patients with low expression of miR‑30a were associated with high histological grade and more lymph node metastasis. Moreover, we found that miR‑30a suppressed TNBC cell epithelial‑mesenchymal transition (EMT), as demonstrated by the overexpression of miR‑30a which increased the expression of epithelial marker E‑cadherin but decreased the expression of mesenchymal markers N‑cadherin and vimentin. Furthermore, we demonstrated that overexpression of miR‑30a significantly suppressed TNBC cell invasion and migration, as well as inhibited tumor growth and metastasis in vivo. More importantly, RTK‑like orphan receptor 1 (ROR1) was predicted as the direct target of miR‑30a, which was subsequently confirmed by luciferase assays. Forced expression of miR‑30a in TNBC cells decreased ROR1 expression, whereas the overexpression of ROR1 reversed the suppressive effects of miR‑30a in TNBC cell migration and invasion. Collectively, this study indicated that miR‑30a functions as a tumor‑metastasis suppressor miRNA in TNBC by directly targeting ROR1 and that miR‑30a may serve as a novel therapeutic target for TNBC.
三阴性乳腺癌（TNBC）是一种侵袭性很强的乳腺癌亚型，缺乏有效的靶向治疗方法。在本研究中，我们揭示了 miR-30a 在 TNBC 中的表达显著降低，并且 miR-30a 低表达的 TNBC 患者与高组织学分级和更多淋巴结转移相关。此外，我们发现 miR-30a 抑制了 TNBC 细胞上皮-间充质转化（EMT），表现为 miR-30a 的过表达增加了上皮标志物 E-钙黏蛋白的表达，同时降低了间充质标志物 N-钙黏蛋白和波形蛋白的表达。此外，我们证明了 miR-30a 的过表达显著抑制了 TNBC 细胞的侵袭和迁移，以及体内肿瘤的生长和转移。更重要的是，RTK 样孤儿受体 1（ROR1）被预测为 miR-30a 的直接靶标，随后通过荧光素酶测定得到了证实。在 TNBC 细胞中强制表达 miR-30a 降低了 ROR1 的表达，而 ROR1 的过表达逆转了 miR-30a 对 TNBC 细胞迁移和侵袭的抑制作用。综上所述，本研究表明，miR-30a 通过直接靶向 ROR1 作为 TNBC 中的肿瘤转移抑制 miRNA 发挥作用，miR-30a 可能成为 TNBC 的一种新的治疗靶点。
