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首页> 外文期刊>Oncology Research >MicroRNA-33b Inhibits the Proliferation and Migration of Osteosarcoma Cells via Targeting Hypoxia-Inducible Factor-1 alpha
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MicroRNA-33b Inhibits the Proliferation and Migration of Osteosarcoma Cells via Targeting Hypoxia-Inducible Factor-1 alpha

机译：MicroRNA-33B通过靶向缺氧诱导因子-1α抑制骨肉瘤细胞的增殖和迁移

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摘要

Recently, microRNA (miR)-33b has been demonstrated to act as a tumor suppressor in osteosarcoma. However, the regulatory mechanism of miR-33b in osteosarcoma cell proliferation and migration remains largely unknown. In this study, real-time PCR showed that miR-33b was significantly downregulated in osteosarcoma tissues compared to their matched adjacent nontumor tissues. Its expression was also decreased in several common osteosarcoma cell lines, including Saos-2, MG63, U2OS, and SW1353, when compared to normal osteoblast cell line hFOB. Overexpression of miR-33b suppressed U2OS cell proliferation and migration. HIF-1 alpha was further identified as a target of miR-33b, and its protein levels were reduced after overexpression of miR33b in U2OS cells. Moreover, overexpression of HIF-1 alpha significantly reversed the suppressive effect of miR33b on U2OS cell proliferation and migration. In addition, HIF-1 alpha was found to be significantly upregulated in osteosarcoma tissues compared to adjacent nontumor tissues, and their expression levels were inversely correlated to the miR-33b levels in osteosarcoma tissues. According to these findings, miR-33b plays a suppressive role in the regulation of osteosarcoma cell proliferation and migration via directly targeting HIF-1 alpha. Therefore, we suggest that the miR-33b/HIF-1 alpha axis may become a promising therapeutic target for osteosarcoma.
机译：最近，MicroRNA（miR）-33b已经证明在骨肉瘤中作为肿瘤抑制剂。然而，骨肉瘤细胞增殖和迁移中m​​iR-33b的调节机制在很大程度上是未知的。在该研究中，与其匹配的相邻的非轨组织相比，实时PCR显示MiR-33B在骨肉瘤组织中显着下调。与正常成骨细胞系HFOB相比，其表达在几种常见的骨肉瘤细胞系中，包括SAOS-2，Mg63，U2OS和SW1353。 MiR-33B的过表达抑制了U2OS细胞增殖和迁移。 HIF-1α进一步鉴定为miR-33b的靶标，在U2OS细胞中的miR33b过表达后，其蛋白质水平降低。此外，HIF-1α的过度表达显着逆转MIR33B对U2OS细胞增殖和迁移的抑制作用。此外，与相邻的不鲁莫组织相比，发现HIF-1α在骨肉瘤组织中显着上调，并且它们的表达水平与骨肉瘤组织中的miR-33b水平相反。根据这些发现，MIR-33B在骨肉瘤细胞增殖和直接靶向HIF-1α的调节中起着抑制作用。因此，我们建议MiR-33B / HIF-1ααα轴可能成为骨肉瘤的有希望的治疗靶标。

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