Li Wentong, Zhai Limin, Zhao Chunling, Lv Shijun
Department of Pathology, Weifang Medical University, Weifang, 261053, Shandong Province, People's Republic of China,
Breast Cancer Res Treat. 2015 Apr;150(3):501-9. doi: 10.1007/s10549-015-3346-y. Epub 2015 Mar 21.
Epithelial-mesenchymal transition (EMT) is a crucial step in epithelial cancer invasion and metastasis. miR-153 has been identified as a key EMT suppressor. Accordingly, this study aimed to determine the possible relation of miR-153 downregulation to EMT through MTDH modulation. The miR-153 and MTDH expression profiles of human breast cancer specimen were determined by qPCR and evaluated by correlation analysis. Cell viability and clonogenic assays were applied to explore the impact of miR-153 on suppression of proliferation and oncogenic potential of breast cancer cells. Cell migration and invasion assays were used for the functional analysis of miR-153 in MCF-7 and MDA-MB-231 cells. Luciferase assay was adopted to identify MTDH as a new direct target of miR-153. Ectopic expression of miR-153 could significantly inhibit tumor growth and impair the migration and invasion of breast cancer cells. Overexpression of miR-153 simultaneously increased E-cadherin, decreased vimentin expression, and downmodulated EMT-associated transcription factors. miR-153 was negatively correlated with MTDH in cell lines and clinical samples. Overexpression of miR-153 significantly suppressed MTDH, as demonstrated by in vitro MTDH 3'-untranslated region luciferase report assay. MTDH is a direct downstream target of miR-153 and is involved in the miR-153-induced suppression of the migration and invasion of breast cancer cells. Our findings indicate that miR-153 functions as a tumor suppressor and miR-153/MTDH link is a promising therapeutic target for breast cancer.
上皮-间质转化（EMT）是上皮性癌侵袭和转移的关键步骤。miR-153已被确定为关键的EMT抑制因子。因此，本研究旨在通过MTDH调控来确定miR-153下调与EMT之间的可能关系。通过qPCR检测人乳腺癌标本中miR-153和MTDH的表达谱，并通过相关性分析进行评估。应用细胞活力和克隆形成试验来探讨miR-153对抑制乳腺癌细胞增殖和致癌潜能的影响。细胞迁移和侵袭试验用于分析miR-153在MCF-7和MDA-MB-231细胞中的功能。采用荧光素酶试验确定MTDH是miR-153的一个新的直接靶点。miR-153的异位表达可显著抑制肿瘤生长，并损害乳腺癌细胞的迁移和侵袭能力。miR-153的过表达同时增加E-钙黏蛋白，降低波形蛋白表达，并下调与EMT相关的转录因子。在细胞系和临床样本中，miR-153与MTDH呈负相关。体外MTDH 3'-非翻译区荧光素酶报告试验表明，miR-153的过表达显著抑制MTDH。MTDH是miR-153的直接下游靶点，参与miR-153诱导的乳腺癌细胞迁移和侵袭抑制。我们的研究结果表明，miR-153作为一种肿瘤抑制因子发挥作用，miR-153/MTDH联系是乳腺癌一个有前景的治疗靶点。
