Aberrant microRNA (miRNA) expression plays a critical role in osteosarcoma (OS) pathogenesis. In this study, we elucidated the involvement of miR-487a in OS and the underlying molecular mechanisms. We found that miR-487a was upregulated in OS clinical samples and cell lines. Knockdown of miR-487a suppressed OS cell growth and invasion and induced apoptosis; however, overexpression of miR-487a promoted OS cell growth and invasion. Accordingly, downregulation of miR-487a significantly suppressed tumor growth of OS xenografts in vivo. Furthermore, B-cell translocation gene 2 (BTG2) mRNA was found to be a novel target of miR-487a. Knockdown of BTG2 using small interfering RNA (siRNA) recapitulated the oncogenic effects of miR-487a, whereas BTG2 overexpression partially reversed these effects. Finally, miR-487a levels were found to be negatively correlated with BTG2 expression in OS clinical samples. Collectively, our data suggest that miR-487a is an oncogenic miRNA in OS and it lowers BTG2 expression.

中文翻译：

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miR-487a通过靶向BTG2 mRNA在骨肉瘤中执行致癌功能。

微小的microRNA（miRNA）表达在骨肉瘤（OS）发病机理中起关键作用。在这项研究中，我们阐明了miR-487a在OS中的参与以及潜在的分子机制。我们发现，miR-487a在OS临床样品和细胞系中上调。抑制miR-487a抑制OS细胞的生长和侵袭并诱导凋亡。但是，miR-487a的过表达促进了OS细胞的生长和侵袭。因此，miR-487a的下调显着抑制了体内OS异种移植物的肿瘤生长。此外，B细胞易位基因2（BTG2发现mRNA是miR-487a的新靶标。使用小干扰RNA（siRNA）抑制BTG2可以概括miR-487a的致癌作用，而BTG2的过表达则部分逆转了这些作用。最后，发现OS临床样品中miR-487a水平与BTG2表达负相关。总体而言，我们的数据表明miR-487a是OS中的致癌miRNA，可降低BTG2的表达。