miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion Journal Article
| Authors: | Chen, D.; Sun, Y.; Yuan, Y.; Han, Z.; Zhang, P.; Zhang, J.; You, M. J.; Teruya-Feldstein, J.; Wang, M.; Gupta, S.; Hung, M. C.; Liang, H.; Ma, L. |
| Article Title: | miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion |
| Abstract: | 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. © 2014 Chen et al. |
| Keywords: | controlled study; unclassified drug; nonhuman; mouse; breast cancer; microrna; gene expression profiling; animal experiment; cell motion; in vivo study; in vitro study; uvomorulin; dna methylation; carcinogenesis; dna; breast tumor; carcinogenicity; cell migration; breast epithelium; down regulation; transcription factor snail; transcription factor twist; cell invasion; cell motility; transcription factor hoxa10; epithelial mesenchymal transition; microrna 125b; microrna 22; female; article; microrna 100; microrna 720; transcription factor zeb1 |
| Journal Title: | PLoS Genetics |
| Volume: | 10 |
| Issue: | 2 |
| ISSN: | 1553-7390 |
| Publisher: | Public Library of Science |
| Date Published: | 2014-02-27 |
| Start Page: | e1004177 |
| Language: | English |
| DOI: | 10.1371/journal.pgen.1004177 |
| PROVIDER: | scopus |
| PMCID: | PMC3937226 |
| PUBMED: | 24586203 |
| DOI/URL: | |
| Notes: | PLoS Genet. -- Export Date: 8 July 2014 -- Source: Scopus |
