Abstract
Osteosarcoma patients with lung metastasis and local invasion remain challenging to treat despite the significant contribution of the combination of surgery and neo-adjuvant chemotherapy. Our previous microarray study demonstrated that miR-302b had significantly lower expression in osteosarcoma cell lines than in osteoblast cell lines. In the present study, we further elucidated the role of miR-302b in regulating the migration and invasiveness of osteosarcoma. MiR-302b expression was markedly down-regulated in osteosarcoma cell lines and clinical tumour tissues. Lower levels of miR-302b expression were significantly associated with metastasis and high pathological grades. A functional study demonstrated that over-expression of miR-302b suppressed tumour cell proliferation, invasion and migration in vitro and in vivo. Runx2 was identified as a direct target gene for miR-302b by bioinformatics analysis and dual-luciferase reporter gene assay. Moreover, over-expression of miR-302b induced down-regulation of Runx2, OPN, MMP-2, MMP-9, MMP-12, MMP-14, and VEGF in 143B cells. Exogenous expression of Runx2 partially rescued the inhibitory effect of miR-302b on the invasion and migration activity of 143B osteosarcoma cells. Taken together, our results indicate that miR-302b functions as a tumour repressor in the invasion and migration of osteosarcoma by directly downregulating Runx2 expression and may be a potential therapeutic target for osteosarcoma.
Highlights
Our previous study demonstrated by miRNA microarrays and bioinformatic analysis that several miRNAs are differentially expressed between osteosarcoma and osteoblast cell lines[10]
We explored the potential function of miR-302b in osteosarcoma cell invasion and migration
The results showed that miR-302b expression levels in the MG-63,U2OS,143B,and Saos[2] cell lines were significantly lower than those in the two osteoblastic cell lines (Fig. 1A).detection of miR-302b expression was performed using quantitative real-time PCR (qRT-PCR) in 31 pairs of human primary osteosarcoma tumours and adjacent normal bone tissues
Summary
Our previous study demonstrated by miRNA microarrays and bioinformatic analysis that several miRNAs are differentially expressed between osteosarcoma and osteoblast cell lines[10]. MiR-302b, one of the 268 dysregulated miRNAs, is significantly under-expressed in osteosarcoma cell lines compared with osteoblast cell lines[10]. The potential function of miR-302b in osteosarcoma metastasis remains obscure. We explored the potential function of miR-302b in osteosarcoma cell invasion and migration. We investigated the potential role of miR-302b in the cell proliferation, invasion, and migration of osteosarcoma cell lines. No underlying molecular mechanism of the function of miR-302b in osteosarcoma by bioinformatics analysis and rescue experiments. The potential role of miR-302b in osteosarcoma was further demonstrated in a nude mouse model. The present study provided a deeper understanding of miR-302b in the development and progression of osteosarcoma
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