Bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-208a promotes osteosarcoma cell proliferation, migration, and invasion
Bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-208a promotes osteosarcoma cell proliferation, migration, and invasion
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DOI：
10.1002/jcp.29351
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发表时间：
2019-10-21
影响因子：
5.6
通讯作者：
Zhu, Jun
中科院分区：
文献类型：
--
作者：
Qin, Fa;Tang, Haoyu;Zhu, Jun
最近的一项研究发现，间充质干细胞（MSC）被招募到肿瘤和MSC衍生的外泌体中，这是人类癌症中细胞间通讯的一种新机制。在这项研究中，我们探讨了来自骨髓间充质干细胞（BMSC）的microRNA-208 a（miR-208 a）富集的外泌体对骨肉瘤细胞的影响。将人骨肉瘤细胞MG-63和Saos-2暴露于用miR-208 a模拟物或抑制剂处理的BMSC来源的外泌体。采用MTT法、transwell迁移实验和软琼脂集落形成实验检测骨肉瘤细胞的存活率、迁移能力和集落形成能力。生物信息学分析和双荧光素酶报告基因分析验证了miR-208 a和PDCD 4之间的靶向关系。Western blot检测PDCD 4及ERK 1/2通路相关蛋白在骨肉瘤细胞中的表达。骨髓基质细胞通过exosomes与骨肉瘤细胞相互作用。miR-208 a的异位表达显示出增加骨肉瘤细胞的存活力、迁移和克隆形成。外泌体含量的分析鉴定了miR-208 a作为外泌体对骨肉瘤细胞作用的介导物，其部分通过下调PDCD 4和激活ERK 1/2途径。综上所述，我们的研究阐明了BMSC来源的外泌体miR-208 a促进骨肉瘤的进展。
A recent study has discovered that mesenchymal stem cells (MSCs) are recruited into tumors and MSC-derived exosomes in a novel mechanism of cell-to-cell communication in human cancers. Here, in this study, we explore the impact of the microRNA-208a (miR-208a)-enriched exosomes derived from bone marrow-derived mesenchymal stem cells (BMSCs) on osteosarcoma cells. Human osteosarcoma cells MG-63 and Saos-2 were exposed to BMSCs-derived exosomes treated with either miR-208a mimic or inhibitor. The MTT assay, transwell migration assay, and soft agar colony formation assay were used to evaluate the viability, migration, and clonogenicity of osteosarcoma cells. Bioinformatics analysis and dual-luciferase reporter gene assays validated the targeted relationship between miR-208a and PDCD4. Western blot assay was used to detect the expression of PDCD4 and related proteins in the ERK1/2 pathway in osteosarcoma cells. BMSCs communicated with osteosarcoma cells via exosomes. Ectopic expression of miR-208a was shown to increase the viability, migration, and clonogenicity of osteosarcoma cells. Analysis of the exosomal content identified miR-208a as a mediator of the exosomal effects on osteosarcoma cells in part via downregulation of PDCD4 and activating the ERK1/2 pathway. In summary, our study illuminates that BMSC-derived exosomal miR-208a enhances the progression of osteosarcoma.