MiR-140 is co-expressed with Wwp2-C transcript and activated by Sox9 to target Sp1 in maintaining the chondrocyte proliferation
MiR-140 is co-expressed with Wwp2-C transcript and activated by Sox9 to target Sp1 in maintaining the chondrocyte proliferation
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MiR-140 与 Wwp2-C 转录物共表达，并被 Sox9 激活以靶向 Sp1 维持软骨细胞增殖
DOI：
10.1016/j.febslet.2011.08.013
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发表时间：
2011-10-03
期刊：
影响因子：
3.5
通讯作者：
Guo, Xizhi
中科院分区：
文献类型：
--
作者：
Yang, Jun;Qin, Shengying;Guo, Xizhi
MiR-140是一种特异性参与软骨形成和骨关节炎发病机制的microRNA。然而，其在软骨发育中的转录调控和靶基因尚未完全了解。在这里，我们检测到miR-140在软骨细胞中唯一表达，并被Wnt/β-catenin信号转导抑制。miR-140的初级转录产物是一种内含子保留的RNA，与Wwp 2-C亚型共表达，Sox 9通过与Wwp 2基因的内含子10结合直接诱导miR-140的表达。肢芽微团培养物中miR-140的敲低导致软骨形成增殖的停滞。Sp1是细胞周期调节因子p15（INK 4 b）的激活因子，是miR-140维持软骨细胞增殖的靶点。总的来说，我们的发现扩展了我们对miR-140在软骨形成中的转录调控和软骨形成作用的理解。(C)2011年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
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.