HOXC10 Regulates Osteogenesis of Mesenchymal Stromal Cells Through Interaction with Its Natural Antisense Transcript lncHOXC-AS3
HOXC10 Regulates Osteogenesis of Mesenchymal Stromal Cells Through Interaction with Its Natural Antisense Transcript lncHOXC-AS3
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HOXC10 通过与其天然反义转录本 lncHOXC-AS3 相互作用调节间充质基质细胞的成骨
DOI：
10.1002/stem.2925
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发表时间：
2019-02-01
期刊：
影响因子：
5.2
通讯作者：
Zhuang, Wenzhuo
中科院分区：
文献类型：
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作者：
Li, Bingzong;Han, Huiying;Zhuang, Wenzhuo
来自多发性骨髓瘤（MM）患者的间充质间质细胞（MSCs）的特征在成骨分化中通常受到损害。然而，潜在的分子机制需要进一步研究。lncrna正在成为致癌途径的关键调控分子。在本研究中，我们发现在MM患者骨髓（BM）来源的MSCs （MM-MSCs）中存在与HOXC10相反转录的具有生物活性的lncRNA HOXC-AS3。HOXC-AS3能够在重叠部位与HOXC10相互作用，这种相互作用增加了HOXC10的稳定性，然后促进其表达，从而抑制MM-MSCs的成骨。在小鼠模型中，静脉注射siHOXC-AS3被证明可以有效预防骨质流失，并通过抗代谢活性和骨形成来维持。这些数据表明，通过增强HOXC10的表达，lncHOXC-AS3是BM-MSCs成骨所必需的。因此，我们的发现揭示了lncRNA HOXC-AS3作为MM骨病治疗靶点的潜在临床意义。37:247 - 256
The characteristics of mesenchymal stromal cells (MSCs) which derived from multiple myeloma (MM) patients are typically impaired in osteogenic differentiation. However, the underlying molecular mechanisms need to be further investigated. lncRNAs are emerging as critical regulation molecules in oncogenic pathways. In this study, we identified that bioactive lncRNA HOXC-AS3, which is transcribed in opposite to HOXC10, was presented in MSCs derived from bone marrow (BM) of MM patients (MM-MSCs). HOXC-AS3 was able to interact with HOXC10 at the overlapping parts and this interaction increased HOXC10 stability, then promoted its expression, conferring osteogenesis repression to MM-MSCs. In mouse models, intravenously administered siHOXC-AS3 was proven to be effective in prevention of bone loss, sustained by both anticatabolic activities and bone-forming. These data showed that lncHOXC-AS3 was required for osteogenesis in BM-MSCs by enhancing HOXC10 expression. Our finding thus unveils a novel insight for the potential clinical significance of lncRNA HOXC-AS3 as a therapeutic target for bone disease in MM. Stem Cells 2019;37:247-256