miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion

PLoS Genet. 2014 Feb 27;10(2):e1004177. doi: 10.1371/journal.pgen.1004177. eCollection 2014 Feb.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Carcinogenesis / genetics*
  • Cdh1 Proteins / biosynthesis
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / biosynthesis
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics*
  • Transcription Factors / biosynthesis


  • Cadherins
  • Cdh1 Proteins
  • FZR1 protein, human
  • Homeodomain Proteins
  • MIRN100 microRNA, human
  • MicroRNAs
  • Transcription Factors
  • homeobox A1 protein