miR-153 inhibits epithelial-mesenchymal transition by targeting metadherin in human breast cancer
miR-153 inhibits epithelial-mesenchymal transition by targeting metadherin in human breast cancer
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DOI：
10.1007/s10549-015-3346-y
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发表时间：
2015-04-01
影响因子：
3.8
通讯作者：
Lv, Shijun
中科院分区：
文献类型：
--
作者：
Li, Wentong;Zhai, Limin;Lv, Shijun
上皮-间质转化（EMT）是上皮癌侵袭和转移的关键步骤。miR-153被认为是一种重要的EMT抑制因子。因此，本研究旨在确定miR-153下调通过MTDH调节与EMT的可能关系。采用qPCR方法检测乳腺癌组织中miR-153和MTDH的表达，并进行相关性分析。应用细胞活力和克隆形成测定来探索miR-153对乳腺癌细胞的增殖抑制和致癌潜力的影响。使用细胞迁移和侵袭测定来分析miR-153在MCF-7和MDA-MB-231细胞中的功能。采用荧光素酶法鉴定MTDH作为miR-153的新的直接靶点。miR-153的异位表达可显著抑制乳腺癌细胞的生长，降低其迁移和侵袭能力。miR-153的过表达同时增加了E-钙粘蛋白，减少了波形蛋白的表达，并下调了EMT相关转录因子。在细胞系和临床样本中，miR-153与MTDH呈负相关。过表达miR-153显著抑制MTDH，如通过体外MTDH 3 '-非翻译区荧光素酶报告测定所证明的。MTDH是miR-153的直接下游靶点，并参与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连接是一个有希望的乳腺癌治疗靶点。
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.