GSE108159
Exosome-mediated transfer of lncRUNX2-AS1 from multiple myeloma cells to MSCs contributes to osteogenesis
Multiple myeloma (MM) is characterized by the impaired osteogenic differentiation of mesenchymal stem cells (MSCs). Stromal communication with cancer cells can influence treatment response. Understanding the cellular interactions within the tumor-bone milieu is critical to the development of novel agents that can reverse bone diseases. Here we identified that bioactive lncRNA RUNX2-AS1 in myeloma cells could be incorporated into exosomes and transmitted to MSCs, thus repressing the osteogenesis of MSCs. RUNX2-AS1, which arises from the antisense strand of RUNX2, was enriched in MSCs derived from MM patients (MM-MSCs). RUNX2-AS1 was capable of forming an RNA duplex with RUNX2 pre-mRNA at overlapping regions and this duplex transcriptionally repressed RUNX2 expression by reducing the splicing efficiency, resulting in decreased osteogenic potential of MSCs. In vivo mouse models, intraperitoneally administered GW4869, an inhibitor of exosome secretion, was found to be effective in prevention of bone loss, sustained by both bone-forming and anticatabolic activities. Therefore, exosomic lncRNA RUNX2-AS1 may serve as a potential therapeutic target for bone lesions in MM. In summary, our results indicated a unique role of exosomic lncRUNX2-AS1 in transferring from MM cells to MSCs in osteogenic differentiation, through a novel exosomic lncRUNX2-AS1/RUNX2 signaling pathway. Overall design: Examination of 6 different expression in 2 cell types.