miR-151-3p Targets TWIST1 to Repress Migration of Human Breast Cancer Cells.
miR-151-3p Targets TWIST1 to Repress Migration of Human Breast Cancer Cells.
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DOI：
10.1371/journal.pone.0168171
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Tseng LM
中科院分区：
文献类型：
--
作者：
Yeh TC;Huang TT;Yeh TS;Chen YR;Hsu KW;Yin PH;Lee HC;Tseng LM
TWIST1是一种高度保守的碱性螺旋-环-螺旋转录因子，通过促进上皮-间质转化和抑制乳腺癌中的E-钙粘蛋白基因表达来促进癌症转移。在这项研究中，我们探讨了 miR-151 在人类乳腺癌细胞中 TWIST1 表达和癌症特性中的潜在作用。我们发现人类 TWIST1 3'UTR 在假定的靶序列 5'-CAGUCUAG-3' 处包含 miR-151-3p 的潜在结合位点。使用 TWIST1-3'UTR 荧光素酶报告基因测定，我们证明 TWIST1 3'UTR 内的靶序列是 miR-151-3p 调节 TWIST1 表达所必需的。此外，我们发现表达miR-151的腺病毒感染后异位表达miR-151-3p可显着降低TWIST1表达、迁移和侵袭，但不影响人乳腺癌细胞的细胞生长和肿瘤球形成。此外，没有 TWIST1 3’UTR 的蛋白质编码区的过表达逆转了 miR-151-3p 对细胞迁移的抑制。此外，敲低 miR-151-3p 会增加 TWIST1 表达，减少 E-钙粘蛋白表达，并增强细胞迁移。总之，这些结果表明miR-151-3p通过靶向TWIST1 3'UTR直接调节TWIST1表达，从而通过增强E-cadherin表达来抑制人乳腺癌细胞的迁移和侵袭。我们的发现进一步证明 microRNA 通过调节 TWIST1 表达参与乳腺癌进展。
TWIST1 is a highly conserved basic helix-loop-helix transcription factor that contributes to cancer metastasis by promoting an epithelial-mesenchymal transition and repressing E-cadherin gene expression in breast cancer. In this study, we explored the potential role of miR-151 in TWIST1 expression and cancer properties in human breast cancer cells. We found that the human TWIST1 3’UTR contains a potential binging site for miR-151-3p at the putative target sequence 5’-CAGUCUAG-3’. Using a TWIST1-3’UTR luciferase reporter assay, we demonstrated that the target sequence within the TWIST1 3’UTR is required for miR-151-3p regulation of TWIST1 expression. Moreover, we found that ectopic expression of miR-151-3p by infection with adenoviruses expressing miR-151 significantly decreased TWIST1 expression, migration and invasion, but did not affect cell growth and tumorsphere formation of human breast cancer cells. In addition, overexpression of the protein coding region without the 3’UTR of TWIST1 reversed the repression of cell migration by miR-151-3p. Furthermore, knockdown of miR-151-3p increased TWIST1 expression, reduced E-cadherin expression, and enhanced cell migration. In conclusion, these results suggest that miR-151-3p directly regulates TWIST1 expression by targeting the TWIST1 3’UTR and thus repressing the migration and invasion of human breast cancer cells by enhancing E-cadherin expression. Our findings add to accumulating evidence that microRNAs are involved in breast cancer progression by modulating TWIST1 expression.
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DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
影响因子：
--
作者：
Liu, Sheng;Cui, Juan;Wan, Guohui
通讯作者：
Wan, Guohui
影响因子：
3.7
作者：
Hernandez, J. M.;Elahi, A.;Shibata, D.
通讯作者：
Shibata, D.
影响因子：
2.9
作者：
McNally, Megan E.;Collins, Amy;Bloomston, Mark
通讯作者：
Bloomston, Mark
影响因子：
11.5
作者：
Hui, Angela B. Y.;Lin, Alice;Liu, Fei-Fei
通讯作者：
Liu, Fei-Fei