Journal
FEBS LETTERS
Volume 585, Issue 19, Pages 2992-2997Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2011.08.013
Keywords
Chondrogenesis; MiR-140; Wwp2; MicroRNA sponge; Sp1
Funding
- National Grand Fundamental Research 973 Program of China [2007CB947301]
- National Natural Science Foundation of China [30800613]
- Pujiang Talent [08PJ1407200]
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MiR-140 is a microRNA specially involved in chondrogenesis and osteoarthritis pathogenesis. However, its transcriptional regulation and target genes in cartilage development are not fully understood. Here we detected that miR-140 was uniquely expressed in chondrocyte and suppressed by Wnt/beta-catenin signalling. The miR-140 primary transcript was an intron-retained RNA co-expressed with Wwp2-C isoform, which was directly induced by Sox9 through binding to the intron 10 of Wwp2 gene. Knockdown of miR-140 in limb bud micromass cultures resulted in arrest of chondrogenic proliferation. Sp1, the activator of the cell cycle regulator p15(INK4b), was identified as a target of miR-140 in maintaining the chondrocyte proliferation. Collectively, our findings expand our understanding of the transcriptional regulation and the chondrogenic role of miR-140 in chondrogenesis. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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