Department of Haematology, The Second Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
Department of Cell Biology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou, People's Republic of China.
Stem Cells. 2019 Feb;37(2):247-256. doi: 10.1002/stem.2925. Epub 2018 Dec 2.
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.
多发性骨髓瘤（MM）患者来源的间充质基质细胞（MSCs）的成骨分化特性通常受损。然而，其潜在的分子机制仍需要进一步研究。lncRNA 作为致癌途径中的关键调节分子而逐渐受到关注。在本研究中，我们鉴定出一种具有生物活性的 lncRNA HOXC-AS3，它与 HOXC10 反义转录，存在于 MM 患者骨髓（BM）来源的 MSCs（MM-MSCs）中。HOXC-AS3 能够与 HOXC10 在重叠部分相互作用，这种相互作用增加了 HOXC10 的稳定性，从而促进其表达，导致 MM-MSCs 的成骨抑制。在小鼠模型中，静脉注射 siHOXC-AS3 被证明在预防骨质流失方面是有效的，这是通过抗分解代谢活性和骨形成来维持的。这些数据表明，lncHOXC-AS3 通过增强 HOXC10 的表达来促进 BM-MSCs 中的成骨作用。因此，我们的发现揭示了 lncRNA HOXC-AS3 作为 MM 骨疾病治疗靶点的潜在临床意义的新见解。干细胞 2019;37:247-256.
