The microRNA-200 family coordinately regulates cell adhesion and proliferation in hair morphogenesis

Jaimee E. Hoefert, Glen A. Bjerke, Dongmei Wang, Rui Yi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

The microRNA (miRNA)-200 (miR-200) family is highly expressed in epithelial cells and frequently lost in metastatic cancer. Despite intensive studies into their roles in cancer, their targets and functions in normal epithelial tissues remain unclear. Importantly, it remains unclear how the two subfamilies of the five-miRNA family, distinguished by a single nucleotide within the seed region, regulate their targets. By directly ligating miRNAs to their targeted mRNA regions, we identify numerous miR-200 targets involved in the regulation of focal adhesion, actin cytoskeleton, cell cycle, and Hippo/Yap signaling. The two subfamilies bind to largely distinct target sites, but many genes are coordinately regulated by both subfamilies. Using inducible and knockout mouse models, we show that the miR-200 family regulates cell adhesion and orientation in the hair germ, contributing to precise cell fate specification and hair morphogenesis. Our findings demonstrate that combinatorial targeting of many genes is critical for miRNA function and provide new insights into miR-200's functions.

Original languageEnglish (US)
Pages (from-to)2185-2204
Number of pages20
JournalJournal of Cell Biology
Volume217
Issue number6
DOIs
StatePublished - Jun 1 2018

ASJC Scopus subject areas

  • Cell Biology

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