Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-01197-w
Keywords
-
Categories
Funding
- SystemsX.ch RTD project Cellplasticity
- SystemsX.ch MTD project MetastasiX
- Swiss National Science Foundation
- Swiss Cancer League
- Swiss National Foundation
Ask authors/readers for more resources
Epithelial tumour cells can gain invasive and metastatic capabilities by undergoing an epithelial-mesenchymal transition. Transcriptional regulators and post-transcriptional effectors like microRNAs orchestrate this process of high cellular plasticity and its malignant consequences. Here, using microRNA sequencing in a time-resolved manner and functional validation, we have identified microRNAs that are critical for the regulation of an epithelial-mesenchymal transition and of mesenchymal tumour cell migration. We report that miR-1199-5p is downregulated in its expression during an epithelial-mesenchymal transition, while its forced expression prevents an epithelial-mesenchymal transition, tumour cell migration and invasion in vitro, and lung metastasis in vivo. Mechanistically, miR-1199-5p acts in a reciprocal double-negative feedback loop with the epithelial-mesenchymal transition transcription factor Zeb1. This function resembles the activities of miR-200 family members, guardians of an epithelial cell phenotype. However, miR-1199-5p and miR-200 family members share only six target genes, indicating that, besides regulating Zeb1 expression, they exert distinct functions during an epithelial-mesenchymal transition.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available