Downregulation of miR-106b induced breast cancer cell invasion and motility in association with overexpression of matrix metalloproteinase 2.
Bottom Line: Breast cancer (BC) is one of the most common cancers in women, and it can often metastasize to the bone.In a previous study, we found the expression of matrix metalloproteinase 2 (MMP2) to be significantly more pronounced at metastatic bone sites than at orthotopic sites.MiR-106b levels in orthotopic tumor tissue showed a negative correlation with MMP2 expression and breast cancer bone metastasis.
Affiliation: Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.Show MeSH
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Mentions: Bioinformatic analysis indicated the presence of a conserved binding site for miR-106b in MMP2 3′UTR (Suppl. Fig. S3). We found the expression level of miR-106b at the cancer site of BC patients to be lower than at the normal site (Fig.2a). The expression level of miR-106b was found to be inversely correlated with MMP2 in MCF-7 and SUM1315-bo cells. MCF-7 cells expressed more miR-106b but less MMP2 than SUM1315-bo cells (Fig.2a, Suppl. Fig. S2c,d). These results suggest a possible role for miR-106b in the regulation of MMP2. We therefore evaluated MMP2 as a target of miR-106b. To validate this hypothesis, we first investigated the effects of miR-106b overexpression on MMP2 mRNA and protein levels in SUM1315-bo cells using real-time PCR and Western blot analysis. As expected, transfection of SUM1315-bo cells with miR-106b significantly decreased MMP2 mRNA and protein levels (Fig.2b). We next investigated the effects of miR-106b-specific inhibitor (miR-106bI) on MMP2 mRNA and protein levels in MCF-7 cells. Again, miR-106bI significantly increased MMP2 mRNA and protein levels in MCF-7 cells (Fig.2b). We then focused on the potential of MMP2 as a target of the events through which miR-106b mediates the invasive and migratory activity of BC cells.
Affiliation: Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.