MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells

被引：49
作者：
Huszar, Jessica M.
Payne, Christopher J.
机构：
[1] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Driskill Grad Program, Chicago, IL 60611 USA
[2] Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Driskill Grad Program, Chicago, IL 60611 USA
[3] Ann & Robert H Lurie Childrens Hosp, Chicago Res Ctr, Human Mol Genet Program, Chicago, IL 60611 USA
来源：
FEBS LETTERS | 2014年 / 588卷 / 09期
关键词：
Stem cells; MicroRNA; Jumonji domain containing 3; MIR146A; Osteogenesis; Cell differentiation; HISTONE DEMETHYLASE JMJD3; OSTEOBLAST DIFFERENTIATION; H3K27; DEMETHYLASE; EZH2; METHYLTRANSFERASE; CANCER; CHROMATIN; PATHWAY; TARGETS; OSTERIX;
D O I：
10.1016/j.febslet.2014.03.057
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Chromatin remodeling is important for cell differentiation. Histone methyltransferase EZH2 and histone demethylase JMJD3 (KDM6B) modulate levels of histone H3 lysine 27 trimethylation (H3K27me3). Interplay between the two modulators influence lineage specification in stem cells. Here, we identified microRNA MIR146A to be a negative regulator of JMJD3. In the osteogenic differentiation of human mesenchymal stem cells (hMSCs), we observed an upregulation of JMJD3 and a downregulation of MIR146A. Blocking JMJD3 activity in differentiating hMSCs reduced transcript levels of osteogenic gene RUNX2. H3K27me3 levels decreased at the RUNX2 promoter during cell differentiation. Modulation of MIR146A levels in hMSCs altered JMJD3 and RUNX2 expression and affected osteogenic differentiation. We conclude that JMJD3 promotes osteogenesis in differentiating hMSCs, with MIR146A regulating JMJD3. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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收藏
页码：1850 / 1856
页数：7
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