An Ning, Luo Xinmei, Zhang Ming, Yu Ruilian
Department of Oncology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Exp Ther Med. 2017 Jan;13(1):79-84. doi: 10.3892/etm.2016.3942. Epub 2016 Dec 1.
Breast cancer is the most common malignant disease in women, and metastasis formed at distant anatomic sites was the major cause of cancer-related mortality. Thus, a novel therapy target and progression biomarker for breast cancer metastasis was necessary. microRNA (miR)-376b has been demonstrated to regulate angiogenesis; however, its role in cancer metastasis remains elusive. In the present study, the expression of miR-376b in normal breast tissue, JC and 4T1 cells was determined by qPCR. Furthermore, and experiments were performed to determine the effect of miR-376b on breast cancer metastasis. The direct target of miR-376b was determined by the luciferase assay and western blotting. The results indicated that silencing of miR-376b by the miR-376-mimic significantly inhibited 4T1 cell migration and invasion . Lung metastasis was also evidently decreased after silencing of miR-376b in 4T1 cells. Moreover, the luciferase assay and western blotting identified that Hoxd10 is the direct target of miR-376b during the regulation of breast cancer metastasis. To the best of our knowledge, the present study was the first to demonstrate the promoting breast cancer metastasis role of miR-376b by directly targeting Hoxd10. Therefore, it would be a novel therapy target and prognostic biomarker for breast cancer.
乳腺癌是女性最常见的恶性疾病，远处解剖部位形成的转移是癌症相关死亡的主要原因。因此，需要一种新的乳腺癌转移治疗靶点和进展生物标志物。微小RNA（miR）-376b已被证明可调节血管生成；然而，其在癌症转移中的作用仍不清楚。在本研究中，通过qPCR测定了miR-376b在正常乳腺组织、JC和4T1细胞中的表达。此外，进行了实验以确定miR-376b对乳腺癌转移的影响。通过荧光素酶测定和蛋白质印迹法确定了miR-376b的直接靶标。结果表明，miR-376模拟物沉默miR-376b可显著抑制4T1细胞迁移和侵袭。4T1细胞中miR-376b沉默后，肺转移也明显减少。此外，荧光素酶测定和蛋白质印迹法确定Hoxd10是miR-376b在调节乳腺癌转移过程中的直接靶标。据我们所知，本研究首次证明miR-376b通过直接靶向Hoxd10促进乳腺癌转移。因此，它将是一种新的乳腺癌治疗靶点和预后生物标志物。
