MicroRNA-9-5p inhibits osteosarcoma cell promotion, metastasis and resistance to apoptosis via negatively targeting Grb2-associated binding protein 2

Abstract

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.