Zhang Haixia, Mai Qing, Chen Juntao
School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, P. R. China.
Center of Regenerative Medicine Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518000, P. R. China.
Cell Biol Int. 2017 Mar;41(3):267-275. doi: 10.1002/cbin.10721. Epub 2017 Jan 6.
Osteosarcoma (OS) is the most common malignant bone tumor and is prevalent in adolescents. In clinical studies, miR-210 has been reported to be tightly correlated to the poor prognosis of OS. Nevertheless, its roles in OS have not been fully elucidated. In view of the central role played by OS stem cells (OSCs) in the malignant progression of OS, this study investigated the influence of miR-210 on the formation of OSCs. Our previous findings suggested that the microenvironment of bone, abundant TGF-β1 and hypoxia, could induce OS cells to dedifferentiate into OSCs. In this study, we found that miR-210 participated in the dedifferentiation of OS cells into OSCs, and inhibiting it significantly suppressed the formation of OSCs. Further results suggested that miR-210 promoted the expression of TGF-β1 and its downstream effectors Snail1 and Slug which were highly elevated in the process of OS dedifferentiation. Additionally, the target gene of miR-210 was also investigated. It was found that NFIC was significantly reduced by miR-210 treatment and also during OS dedifferentiation. Therefore, this study suggested that miR-210 promoted OS cells dedifferentiation and uncovered its role in the malignant progress of OS.
骨肉瘤（OS）是最常见的恶性骨肿瘤，在青少年中高发。在临床研究中，据报道miR-210与骨肉瘤的不良预后密切相关。然而，其在骨肉瘤中的作用尚未完全阐明。鉴于骨肉瘤干细胞（OSCs）在骨肉瘤恶性进展中所起的核心作用，本研究探讨了miR-210对骨肉瘤干细胞形成的影响。我们之前的研究结果表明，富含转化生长因子-β1（TGF-β1）和缺氧的骨微环境可诱导骨肉瘤细胞去分化为骨肉瘤干细胞。在本研究中，我们发现miR-210参与了骨肉瘤细胞向骨肉瘤干细胞的去分化过程，抑制它可显著抑制骨肉瘤干细胞的形成。进一步的结果表明，miR-210促进了TGF-β1及其下游效应因子Snail1和Slug的表达，这些因子在骨肉瘤去分化过程中高度上调。此外，还研究了miR-210的靶基因。结果发现，miR-210处理以及在骨肉瘤去分化过程中，NFIC均显著降低。因此，本研究表明miR-210促进了骨肉瘤细胞的去分化，并揭示了其在骨肉瘤恶性进展中的作用。
