The study explores the inhibition effects of MicroRNAs in osteosarcoma, as a means of suggesting it as treatment for bone cancer. MicroRNAs (miRNAs) are a sort of noncoding RNA molecules that regulates gene expression by targeting mRNAs and play critical roles in tumor development. This study probed the effect of miR-9-5p on osteosarcoma development. Human osteosarcoma cell lines U2-OS, 143B, MG63 and HOS and normal human osteoblast cell line hFOB were cultivated and expression of miR-9-5p and Grb2-associated binding protein 2 (Gab2) measured. The binding of miR-9-5p and Gab2 was confirmed using a bio-information program and dual luciferase reporter gene assay. Loss-of-functions of miR-9-5p and Gab2 were performed to measure their roles in osteosarcoma cell proliferation, invasion, migration and resistance to death. Result showed high miR-9-5p expression and low Gab2 expression in osteosarcoma cells, particularly in U2-OS cells. miR-9-5p directly bound to the 3¢untranslated region of Gab2. Down-regulated miR-9-5p induced U2-OS cell proliferation, invasion and the resistance to death, while conversely, silenced Gab2 led to an opposite trend on U2-OS cell growth and metastasis. Moreover, co-effect of inhibited miR-9-5p and silenced Gab2 led to decreased cell proliferation but promoted cell apoptosis compared to inhibited miR-9-5p alone, while it led to enhanced cell proliferation and invasion, but reduced cell apoptosis compared to silenced Gab2 alone. To conclude, this study demonstrated that miR-9-5p could inhibit osteosarcoma cell proliferation, invasion, migration and resistance to death via negatively targeting Gab2.

中文翻译：

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MicroRNA-9-5p通过负向靶向Grb2相关结合蛋白2抑制骨肉瘤细胞的增殖，转移和抗凋亡

这项研究探索了MicroRNA在骨肉瘤中的抑制作用，作为暗示其可用于治疗骨癌的手段。MicroRNA（miRNA）是一种非编码RNA分子，可通过靶向mRNA来调节基因表达并在肿瘤发展中发挥关键作用。这项研究探讨了miR-9-5p对骨肉瘤发展的影响。培养人骨肉瘤细胞系U2-OS，143B，MG63和HOS以及正常人成骨细胞系hFOB，并检测miR-9-5p和与Grb2相关的结合蛋白2（Gab2）的表达。miR-9-5p和Gab2的结合已通过生物信息程序和双重萤光素酶报告基因检测得到证实。进行miR-9-5p和Gab2的功能丧失，以测量它们在骨肉瘤细胞增殖，侵袭，迁移和抗死亡中的作用。结果显示在骨肉瘤细胞中，特别是在U2-OS细胞中，miR-9-5p表达高而Gab2表达低。miR-9-5p直接结合到Gab2的3′非翻译区。下调的miR-9-5p诱导U2-OS细胞增殖，侵袭和对死亡的抵抗力，相反，沉默的Gab2导致U2-OS细胞生长和转移的相反趋势。而且，与单独抑制miR-9-5p相比，抑制miR-9-5p和沉默的Gab2的共同作用导致细胞增殖减少，但促进细胞凋亡，而与抑制miR-9-5p相比，则导致细胞增殖和侵袭增强，但细胞凋亡减少。沉默了Gab2。总而言之，这项研究表明，miR-9-5p可以通过负向靶向Gab2来抑制骨肉瘤细胞的增殖，侵袭，迁移和对死亡的抵抗力。