Abstract
MicroRNAs serve crucial functions in cancer progression by inhibiting the translation of target genes and causing mRNA degradation. However, the underlying regulatory mechanism of Let-7b in osteosarcoma (OS) has not, to the best of our knowledge, been comprehensively elucidated. The aim of the present study was to investigate the function of Let-7b in OS and clarify the regulation of insulin-like growth factor 1 receptor (IGF1R) by Let-7b. It was observed that Let-7b was significantly downregulated in OS tissues and cell lines compared with the matched adjacent non-tumorous tissues and human normal osteoblastic cell line hFOB 1.19. Overexpression of Let-7b significantly inhibited the proliferation and invasion of U2OS and SAOS-2 cells. A luciferase reporter assay validated that IGF1R was a downstream and functional target of Let-7b. Let-7b was also able to decrease the expression levels of IGF1R protein. Functional studies revealed that the antitumor effect of Let-7b was probably due to targeting and suppressing IGF1R expression. Furthermore, in OS tissues, IGF1R was identified to be significantly upregulated and negatively correlated with Let-7b levels. In conclusion, the results of the present study indicated that Let-7b suppresses OS cellular proliferation and invasion via targeting IGF1R. A novel candidate prognostic factor was identified and it is suggested that the Let-7b/IGF1R axis may represent a novel anti-metastasis therapeutic target in OS.