miR-322 stabilizes MEK1 expression to inhibit RAF/MEK/ERK pathway activation in cartilage

Publikationen: Beitrag in FachzeitschriftZeitschriftenaufsätzeForschungBegutachtung


  • Björn Bluhm
  • Harald W A Ehlen
  • Tatjana Holzer
  • Veronika S Georgieva
  • Juliane Heilig
  • Lena Pitzler
  • Julia Etich
  • Toman Bortecen
  • Christian Frie
  • Kristina Probst
  • Anja Niehoff
  • Daniele Belluoccio
  • Jocelyn Van den Bergen
  • Bent Brachvogel



Cartilage originates from mesenchymal cell condensations that differentiate into chondrocytes of transient growth plate cartilage or permanent cartilage of the articular joint surface and trachea. MicroRNAs fine-tune the activation of entire signaling networks and thereby modulate complex cellular responses, but so far only limited data are available on miRNAs that regulate cartilage development. Here, we characterize a miRNA that promotes the biosynthesis of a key component in the RAF/MEK/ERK pathway in cartilage. Specifically, by transcriptome profiling we identified miR-322 to be upregulated during chondrocyte differentiation. Among the various miR-322 target genes in the RAF/MEK/ERK pathway, only Mek1 was identified as a regulated target in chondrocytes. Surprisingly, an increased concentration of miR-322 stabilizes Mek1 mRNA to raise protein levels and dampen ERK1/2 phosphorylation, while cartilage-specific inactivation of miR322 in mice linked the loss of miR-322 to decreased MEK1 levels and to increased RAF/MEK/ERK pathway activation. Such mice died perinatally due to tracheal growth restriction and respiratory failure. Hence, a single miRNA can stimulate the production of an inhibitory component of a central signaling pathway to impair cartilage development.

ZeitschriftDevelopment (Cambridge, England)
Seiten (von - bis)3562-3577
PublikationsstatusVeröffentlicht - 01.10.2017

ID: 3123178


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