Liang Zhongxing, Bian Xuehai, Shim Hyunsuk
Department of Radiology, Emory University, Atlanta, GA 30322, USA; Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
Department of Radiology, Emory University, Atlanta, GA 30322, USA; Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
Biochem Biophys Res Commun. 2016 Aug 26;477(3):461-6. doi: 10.1016/j.bbrc.2016.06.076. Epub 2016 Jun 16.
Triple negative breast tumors don't respond to Tamoxifen and Herceptin, two of the most effective medications for treating breast cancer. Additionally, triple negative breast cancer (TNBC) intrinsically resists or will eventually acquire resistance to chemotherapy. The purpose of this study is to understand better the molecular basis of TNBC as well as develop new therapeutic strategies against it. Here, we analyzed miRNA-206 expression levels in breast cancer cell lines and tissues. In addition, we investigated whether miR-206 mimics inhibited TNBC tumor invasion and angiogenesis. The results showed that miR-206 was downregulated in TNBC compared to non-TNBC cell lines and tissues. Additionally, the decreased levels of miR-206 were inversely consistent with expression levels of VEGF. Furthermore, the forced expression of miR-206 in the mimic-transfected TNBC cells downregulated VEGF, MAPK3, and SOX9 expression levels. The miR-206 mimics inhibited TNBC breast cell invasion and angiogenesis. These findings demonstrate for the first time the involvement of miRNA-206 in TNBC invasion and angiogenesis and suggest that miR-206 may be an efficient agent for therapy of TNBC.
三阴性乳腺癌对他莫昔芬和赫赛汀这两种治疗乳腺癌最有效的药物均无反应。此外,三阴性乳腺癌(TNBC)本质上对化疗耐药或最终会产生耐药性。本研究的目的是更好地了解TNBC的分子基础,并开发针对它的新治疗策略。在此,我们分析了乳腺癌细胞系和组织中miRNA-206的表达水平。此外,我们研究了miR-206模拟物是否抑制TNBC肿瘤侵袭和血管生成。结果显示,与非TNBC细胞系和组织相比,miR-206在TNBC中表达下调。此外,miR-206水平的降低与VEGF的表达水平呈负相关。此外,在模拟物转染的TNBC细胞中强制表达miR-206可下调VEGF、MAPK3和SOX9的表达水平。miR-206模拟物抑制TNBC乳腺癌细胞的侵袭和血管生成。这些发现首次证明了miRNA-206参与TNBC的侵袭和血管生成,并表明miR-206可能是治疗TNBC的有效药物。