Dicer1 downregulation by multiple myeloma cells promotes the senescence and tumor-supporting capacity and decreases the differentiation potential of mesenchymal stem cells.
Dicer1 downregulation by multiple myeloma cells promotes the senescence and tumor-supporting capacity and decreases the differentiation potential of mesenchymal stem cells.
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多发性骨髓瘤细胞下调Dicer1促进衰老和肿瘤支持能力并降低间充质干细胞的分化潜力
DOI：
10.1038/s41419-018-0545-6
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发表时间：
2018-05-01
影响因子：
9
通讯作者：
Chang C
中科院分区：
文献类型：
--
作者：
Guo J;Zhao Y;Fei C;Zhao S;Zheng Q;Su J;Wu D;Li X;Chang C
骨髓间充质干细胞（BMMSC）促进多发性骨髓瘤（MM）细胞的生长，但其潜在机制仍不清楚。这项研究表明，MM-MSC 的衰老显着增加，表现为增殖减少和衰老相关 β-半乳糖苷酶活性呈阳性的细胞数量增加。衰老的MM-MSCs表现出分化潜力下降和肿瘤支持能力增加。健康对照组 MSC 中 Dicer1 的敲除促进了细胞衰老和肿瘤支持能力，同时降低了分化能力。 Dicer1 在 MM-MSC 中的过度表达逆转了对分化的影响并减少了细胞衰老。此外，microRNA-17家族表达的降低被认为是促进衰老的有利因素，在Dicer1敲除细胞中p21的表达增加。此外，我们观察到 MM-MSC 中 miR-93 和 miR-20a 的表达降低，而 miR-93/miR-20a 的上调则减少细胞衰老，p21 表达增加证明了这一点。重要的是，我们发现，从 Dicer1 和 miR-93/miR-20a 表达降低以及 p21 表达增加观察到，骨髓瘤细胞可以诱导健康对照的 MSC 衰老。总体而言，MM 细胞下调 MSC 中的 Dicer1，从而导致衰老；反过来，衰老的 MSC 会促进 MM 细胞生长，这很可能会导致疾病进展。
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 ofp21increased 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 increasedp21expression. 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 ofp21. 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.
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多发性骨髓瘤骨髓间充质基质细胞早期衰老的证据。
影响因子：
3.7
作者：
André T;Meuleman N;Stamatopoulos B;De Bruyn C;Pieters K;Bron D;Lagneaux L
通讯作者：
Lagneaux L
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
5.6
作者：
Inukai, Sachi;Slack, Frank
通讯作者：
Slack, Frank
影响因子：
7.3
作者：
Gibcus, Johan H.;Kroesen, Bart-Jan;van den Berg, Anke
通讯作者：
van den Berg, Anke
低风险骨髓增生异常综合征患者骨髓间充质干细胞的成骨分化受损
影响因子：
--
作者：
Fei, Chengming;Zhao, Youshan;Chang, Chunkang
通讯作者：
Chang, Chunkang