miR-141-3p inhibits human stromal (mesenchymal) stem cell proliferation and differentiation
miR-141-3p inhibits human stromal (mesenchymal) stem cell proliferation and differentiation
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DOI：
10.1016/j.bbamcr.2014.06.004
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发表时间：
2014-09-01
影响因子：
5.1
通讯作者：
Kassem, Moustapha
中科院分区：
文献类型：
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作者：
Qiu, Weimin;Kassem, Moustapha
Wnt信号传导决定人间质干细胞（hMSC）向成骨细胞或脂肪细胞谱系的分化命运。microRNA（miRNAs）是一种21-25个核苷酸的小RNA分子，调节成骨细胞生物学的许多方面。因此，我们检查了hMSC中由Wnt信号传导调节的miRNA。我们鉴定了miRNA（miR）-141-3p作为Wnt靶标，其反过来抑制Wnt信号传导。此外，miR-141- 3 p通过将细胞阻滞在细胞周期的G1期来抑制hMSC增殖。miR-141- 3 p抑制hMSC的成骨细胞分化，如通过降低碱性磷酸酶活性、基因表达和体外矿化基质形成所证明的。生物信息学研究、Western blot分析和3 'UTR报告基因分析表明，细胞分裂周期25 A（CDC 25 A）是miR-141- 3 p的直接靶点。siRNA介导的CDC 25 A敲低抑制hMSC增殖和成骨细胞分化。总之，miR-141- 3 p作为hMSC增殖和成骨细胞分化的负调节因子。靶向miR-141- 3 p可用作低骨量疾病（例如骨质疏松症）的合成代谢疗法。(C)2014爱思唯尔有限公司版权所有。
Wnt signaling determines human stromal (mesenchymal) stem cell (hMSC) differentiation fate into the osteoblast or adipocyte lineage. microRNAs (miRNAs) are small RNA molecules of 21-25 nucleotides that regulate many aspects of osteoblast biology. Thus, we examined miRNAs regulated by Wnt signaling in hMSC We identified miRNA (miR)-141-3p as a Wnt target which in turn inhibited Wnt signaling. Moreover, miR-141-3p inhibited hMSC proliferation by arresting cells at the G1 phase of the cell cycle. miR-141-3p inhibited osteoblast differentiation of hMSC as evidenced by reduced alkaline phosphatase activity, gene expression and in vitro mineralized matrix formation. Bioinformatic studies, Western blot analysis and 3'UTR reporter assay demonstrated that cell division cycle 25A (CDC25A) is a direct target of miR-141-3p. siRNA-mediated knock-down of CDC25A inhibited hMSC proliferation and osteoblast differentiation. In summary, miR-141-3p acts as a negative regulator of hMSC proliferation and osteoblast differentiation. Targeting miR-141-3p could be used as an anabolic therapy of low bone mass diseases, e.g. osteoporosis. (C) 2014 Elsevier B.V. All rights reserved.