Exosomal miR-21-5p derived from bone marrow mesenchymal stem cells promote osteosarcoma cell proliferation and invasion by targeting PIK3R1.
Exosomal miR-21-5p derived from bone marrow mesenchymal stem cells promote osteosarcoma cell proliferation and invasion by targeting PIK3R1.
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骨髓间充质干细胞来源的外泌体miR-21-5p通过靶向PIK3R1促进骨肉瘤细胞增殖和侵袭
DOI：
10.1111/jcmm.17024
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发表时间：
2021-12
影响因子：
5.3
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Qi J;Zhang R;Wang Y
间充质干细胞（MSC）是一类多能细胞，可以释放大量外泌体，在肿瘤相关微环境中充当旁分泌介质。然而，间充质干细胞衍生的外泌体在癌细胞尤其是骨肉瘤的发病机制和进展中的作用至今尚未彻底阐明。在本研究中，我们建立了人骨髓来源的间充质干细胞与骨肉瘤细胞的共培养模型，然后从诱导的间充质干细胞中提取外泌体，并研究间充质干细胞来源的外泌体在骨肉瘤细胞进展中的作用。本研究的目的是解决间充质干细胞和骨肉瘤细胞之间潜在的细胞生物学效应。结果表明，MSC来源的外泌体可以显着促进骨肉瘤细胞的增殖和侵袭。我们还通过定量实时聚合酶链反应（qRT-PCR）发现，与人胎儿成骨细胞 hFOB1.19 相比，miR-21-5p 在 MSC 和 MSC 衍生的外泌体中显着过度表达。转染miR-21-5p的MSC衍生的外泌体可以在体外和体内显着增强骨肉瘤细胞的增殖和侵袭。生物信息学分析和双荧光素酶报告基因检测验证了外泌体 miR-21-5p 和 PIK3R1 之间的靶向关系；我们进一步证明，来自人骨髓 MSC 的 miR-21-5p 丰富的外泌体可以通过抑制骨肉瘤细胞中 PIK3R1 的表达来激活 PI3K/Akt/mTOR 通路。总之，我们的研究为肿瘤相关微环境中人骨髓间充质干细胞与骨肉瘤细胞之间的相互作用提供了新的见解。
Mesenchymal stem cells (MSCs) are a class of pluripotent cells that can release a large number of exosomes which act as paracrine mediators in tumour‐associated microenvironment. However, the role of MSC‐derived exosomes in pathogenesis and progression of cancer cells especially osteosarcoma has not been thoroughly clarified until now. In this study, we established a co‐culture model for human bone marrow‐derived MSCs with osteosarcoma cells, then extraction of exosomes from induced MSCs and study the role of MSC‐derived exosomes in the progression of osteosarcoma cell. The aim of this study was to address potential cell biological effects between MSCs and osteosarcoma cells. The results showed that MSC‐derived exosomes can significantly promote osteosarcoma cells’ proliferation and invasion. We also found that miR‐21‐5p was significantly over‐expressed in MSCs and MSC‐derived exosomes by quantitative real‐time polymerase chain reaction (qRT‐PCR), compared with human foetal osteoblastic cells hFOB1.19. MSC‐derived exosomes transfected with miR‐21‐5p could significantly enhance the proliferation and invasion of osteosarcoma cells in vitro and in vivo. Bioinformatics analysis and dual‐luciferase reporter gene assays validated the targeted relationship between exosomal miR‐21‐5p and PIK3R1; we further demonstrated that miR‐21‐5p‐abundant exosomes derived human bone marrow MSCs could activate PI3K/Akt/mTOR pathway by suppressing PIK3R1 expression in osteosarcoma cells. In summary, our study provides new insights into the interaction between human bone marrow MSCs and osteosarcoma cells in tumour‐associated microenvironment.
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