Exosomal miR-1228 From Cancer-Associated Fibroblasts Promotes Cell Migration and Invasion of Osteosarcoma by Directly Targeting SCAI.
Exosomal miR-1228 From Cancer-Associated Fibroblasts Promotes Cell Migration and Invasion of Osteosarcoma by Directly Targeting SCAI.
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DOI：
10.3727/096504018x15336368805108
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发表时间：
2019-09-23
影响因子：
3.1
通讯作者：
Jiang XH
中科院分区：
文献类型：
--
作者：
Wang JW;Wu XF;Gu XJ;Jiang XH
癌症相关成纤维细胞（CAF）在调节肿瘤进展中起主要作用。了解CAFs如何与骨肉瘤沟通对于开发新的骨肉瘤治疗方法至关重要。外泌体能够在细胞之间传递信息。在这项研究中，我们证明了CAFs将外泌体转移到骨肉瘤细胞中，从而促进骨肉瘤细胞的迁移和侵袭。使用miRNA微阵列分析，我们鉴定了13种在源自癌症相关成纤维细胞（CAF）和相应癌旁成纤维细胞（PAF）的外来体中显著增加的miRNA。体外研究进一步证实，microRNA-1228（miR-1228）在CAFs及其分泌的exosomes和受体骨肉瘤细胞中表达增加，可下调骨肉瘤内源性SCAI mRNA和蛋白水平。此外，我们的研究结果表明，SCAI在骨肉瘤组织中下调。总之，这项研究提供了证据表明CAF外泌体miR-1228能够通过靶向SCAI促进骨肉瘤侵袭和迁移，这可能代表骨肉瘤治疗的关键治疗靶点。
Cancer-associated fibroblasts (CAFs) play a predominant role in regulating tumor progression. Understanding how CAFs communicate with osteosarcoma is crucial for developing novel approaches for osteosarcoma therapy. Exosomes are able to transmit messages between cells. In this study, we demonstrated that CAFs transfer exosomes to osteosarcoma cells, which promotes osteosarcoma cell migration and invasion. Using a miRNA microarray analysis, we identified 13 miRNAs that are significantly increased in exosomes derived from cancer-associated fibroblasts (CAFs) and corresponding paracancer fibroblasts (PAFs). In vitro studies further validated that the levels of microRNA-1228 (miR-1228) were increased in CAFs, its secreted exosomes, and in recipient osteosarcoma cells, which can downregulate endogenous SCAI mRNA and protein level in osteosarcoma. Furthermore, our findings demonstrate that SCAI was downregulated in osteosarcoma tissues. Taken together, this study provides evidence that CAF exosomal miR-1228 is able to promote osteosarcoma invasion and migration by targeting SCAI, which may represent a critical therapeutic target for osteosarcoma treatment.