miR-100 Induces Epithelial-Mesenchymal Transition but Suppresses Tumorigenesis, Migration and Invasion

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

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

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.

Original languageEnglish
Article numbere1004177
JournalPLoS Genetics
Volume10
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

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