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Published on: February 21, 2014
The microRNA-200 family coordinately regulates cell adhesion and proliferation in hair morphogenesis
Jaimee E Hoefert1, Glen A Bjerke1, Dongmei Wang1
1Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO.
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.
Insights
The microRNA-200 (miR-200) family regulates normal epithelial cell behavior and hair development. This study reveals its targets and functions, highlighting combinatorial gene regulation critical for miRNA activity.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cancer Biology
Background:
- The microRNA (miRNA)-200 (miR-200) family is crucial in epithelial cells but its role in normal tissues is unclear.
- Understanding miR-200's targets and functions, especially the distinct roles of its subfamilies, is essential.
Purpose of the Study:
- To identify miR-200 targets and elucidate its functions in normal epithelial tissues.
- To investigate how the two miR-200 subfamilies regulate targets and contribute to biological processes.
Main Methods:
- Direct ligation of miRNAs to targeted mRNA regions to identify binding sites.
- Utilizing inducible and knockout mouse models to study miR-200 family function in vivo.
Main Results:
- Identified numerous miR-200 targets involved in focal adhesion, cytoskeleton, cell cycle, and Hippo/Yap signaling.
- Demonstrated that miR-200 subfamilies bind to distinct sites but often coordinately regulate genes.
- Showed miR-200 family regulates cell adhesion and orientation in the hair germ, impacting cell fate and hair morphogenesis.
Conclusions:
- Combinatorial targeting of multiple genes is vital for miRNA function.
- Provided new insights into the functions of the miR-200 family in normal epithelial development and morphogenesis.
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