Dicer1 downregulation by multiple myeloma cells promotes the senescence and tumor-supporting capacity and decreases the differentiation potential of mesenchymal stem cells
| Autor: | Chunkang Chang, Youshan Zhao, Qingqing Zheng, Sida Zhao, Jiying Su, Juan Guo, Chengming Fei, Xiao Li, Dong Wu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Senescence Adult Cyclin-Dependent Kinase Inhibitor p21 Male Ribonuclease III Cancer Research Cellular differentiation Immunology Plasma Cells Apoptosis Biology Article DEAD-box RNA Helicases 03 medical and health sciences Cellular and Molecular Neuroscience Downregulation and upregulation Humans lcsh:QH573-671 RNA Small Interfering Cellular Senescence Aged Cell Proliferation Neoplasm Staging Regulation of gene expression Aged 80 and over Gene knockdown Cell growth lcsh:Cytology Mesenchymal stem cell Cell Cycle Cell Differentiation Mesenchymal Stem Cells Cell Biology Middle Aged beta-Galactosidase Coculture Techniques Cell biology Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Case-Control Studies Female Signal transduction Multiple Myeloma Signal Transduction |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 9, Iss 5, Pp 1-15 (2018) |
| ISSN: | 2041-4889 |
| Popis: | Bone marrow mesenchymal stem cells (BMMSCs) facilitate the growth of multiple myeloma (MM) cells, but the underlying mechanisms remain unclear. This study demonstrates that the senescence of MM-MSCs significantly increased, as evidenced by a decrease in proliferation and increase in the number of cells positive for senescence-associated β-galactosidase activity. Senescent MM-MSCs displayed decreased differentiation potential and increased tumor-supporting capacity. Dicer1 knockdown in the MSCs of healthy controls promoted cellular senescence and tumor-supporting capacity, while decreasing the differentiation capacity. Dicer1 overexpression in MM-MSCs reversed the effects on differentiation and reduced cellular senescence. In addition, decreased expression of the microRNA-17 family was identified as a favorable element responsible for increasing senescence, with the expression of p21 increased in Dicer1 knockdown cells. Furthermore, we observed decreased expression of miR-93 and miR-20a in MM-MSCs, while upregulation of miR-93/miR-20a decreased cellular senescence, as evidenced by the increased p21 expression. Importantly, we found that myeloma cells could induce the senescence of MSCs from healthy controls, as observed from the decreased expression of Dicer1 and miR-93/miR-20a and increased expression of p21. Overall, MM cells downregulate Dicer1 in MSCs, which leads to senescence; in turn, senescent MSCs promote MM cell growth, which most likely contributes to disease progression. |
| Databáze: | OpenAIRE |
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