Background: Osteosarcoma (OS) is a prevalent primary bone malignancy and its distal metastasis
remains the main cause of mortality in OS patients. MicroRNAs (miRNAs) play critical roles during cancer
Objective: Thus, elucidating the role of miRNA dysregulation in OS metastasis may provide novel therapeutic
Methods: The previous study found a low miR-134 expression level in the OS specimens compared with paracancer
tissues. Overexpression of miR-134 stable cell lines was established. Cell viability assay, cell invasion
and migration assay and apoptosis assay were performed to evaluate the role of miR-134 in OS in vitro.
Results: We found that miR-134 overexpression inhibits cell proliferation, migration and invasion, and induces
cell apoptosis in both MG63 and Saos-2 cell lines. Mechanistically, miR-134 targets the 3'-UTR of VEGFA and
MYCN mRNA to silence its translation, which was confirmed by luciferase-reporter assay. The real-time PCR
analysis illustrated that miR-134 overexpression decreases VEGFA and MYCN mRNA levels. Additionally, the
overexpression of VEGFA or MYCN can partly attenuate the effects of miR-134 on OS cell migration and
viability. Furthermore, the overexpression of miR-134 dramatically inhibits tumor growth in the human OS cell
line xenograft mouse model in vivo. Moreover, bioinformatic and luciferase assays indicate that the expression
of miR-134 is regulated by Interferon Regulatory Factor (IRF1), which binds to its promoter and activates
Conclusion: Our study demonstrates that IRF1 is a key player in the transcriptional control of miR-134, and it
inhibits cell proliferation, invasion and migration in vitro and in vivo via targeting VEGFA and MYCN.