miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion.
Whether epithelial-mesenchymal transition (EMT) is always linked to increased tumorigenicity is controversial. Through microRNA (miRNA) expression profiling of mammary epithelial cells overexpressing Twist, Snail or ZEB1, we identified miR-100 as a novel EMT inducer. Surprisingly, miR-100 inhibits t...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-02-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1004177&type=printable |
| _version_ | 1826799254562144256 |
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| author | Dahu Chen Yutong Sun Yuan Yuan Zhenbo Han Peijing Zhang Jinsong Zhang M James You Julie Teruya-Feldstein Min Wang Sumeet Gupta Mien-Chie Hung Han Liang Li Ma |
| author_facet | Dahu Chen Yutong Sun Yuan Yuan Zhenbo Han Peijing Zhang Jinsong Zhang M James You Julie Teruya-Feldstein Min Wang Sumeet Gupta Mien-Chie Hung Han Liang Li Ma |
| author_sort | Dahu Chen |
| collection | DOAJ |
| description | Whether epithelial-mesenchymal transition (EMT) is always linked to increased tumorigenicity is controversial. Through microRNA (miRNA) expression profiling of mammary epithelial cells overexpressing Twist, Snail or ZEB1, we identified miR-100 as a novel EMT inducer. Surprisingly, miR-100 inhibits the tumorigenicity, motility and invasiveness of mammary tumor cells, and is commonly downregulated in human breast cancer due to hypermethylation of its host gene MIR100HG. The EMT-inducing and tumor-suppressing effects of miR-100 are mediated by distinct targets. While miR-100 downregulates E-cadherin by targeting SMARCA5, a regulator of CDH1 promoter methylation, this miRNA suppresses tumorigenesis, cell movement and invasion in vitro and in vivo through direct targeting of HOXA1, a gene that is both oncogenic and pro-invasive, leading to repression of multiple HOXA1 downstream targets involved in oncogenesis and invasiveness. These findings provide a proof-of-principle that EMT and tumorigenicity are not always associated and that certain EMT inducers can inhibit tumorigenesis, migration and invasion. |
| first_indexed | 2024-12-21T10:06:43Z |
| format | Article |
| id | doaj.art-1689f83f10564425a660e663a274b3d6 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2025-03-17T00:32:10Z |
| publishDate | 2014-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-1689f83f10564425a660e663a274b3d62025-02-21T05:34:32ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-02-01102e100417710.1371/journal.pgen.1004177miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion.Dahu ChenYutong SunYuan YuanZhenbo HanPeijing ZhangJinsong ZhangM James YouJulie Teruya-FeldsteinMin WangSumeet GuptaMien-Chie HungHan LiangLi MaWhether epithelial-mesenchymal transition (EMT) is always linked to increased tumorigenicity is controversial. Through microRNA (miRNA) expression profiling of mammary epithelial cells overexpressing Twist, Snail or ZEB1, we identified miR-100 as a novel EMT inducer. Surprisingly, miR-100 inhibits the tumorigenicity, motility and invasiveness of mammary tumor cells, and is commonly downregulated in human breast cancer due to hypermethylation of its host gene MIR100HG. The EMT-inducing and tumor-suppressing effects of miR-100 are mediated by distinct targets. While miR-100 downregulates E-cadherin by targeting SMARCA5, a regulator of CDH1 promoter methylation, this miRNA suppresses tumorigenesis, cell movement and invasion in vitro and in vivo through direct targeting of HOXA1, a gene that is both oncogenic and pro-invasive, leading to repression of multiple HOXA1 downstream targets involved in oncogenesis and invasiveness. These findings provide a proof-of-principle that EMT and tumorigenicity are not always associated and that certain EMT inducers can inhibit tumorigenesis, migration and invasion.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1004177&type=printable |
| spellingShingle | Dahu Chen Yutong Sun Yuan Yuan Zhenbo Han Peijing Zhang Jinsong Zhang M James You Julie Teruya-Feldstein Min Wang Sumeet Gupta Mien-Chie Hung Han Liang Li Ma miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion. PLoS Genetics |
| title | miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion. |
| title_full | miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion. |
| title_fullStr | miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion. |
| title_full_unstemmed | miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion. |
| title_short | miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion. |
| title_sort | mir 100 induces epithelial mesenchymal transition but suppresses tumorigenesis migration and invasion |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1004177&type=printable |
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