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Downregulation of miR-106b induced breast cancer cell invasion and motility in association with overexpression of matrix metalloproteinase 2.

Ni X, Xia T, Zhao Y, Zhou W, Wu N, Liu X, Ding Q, Zha X, Sha J, Wang S - Cancer Sci. (2013)

Bottom Line: MMP2 was shown to be a direct target of miR-106b.Both gain- and loss-of-function studies showed that MMP2 could promote the migration and invasion of BC cells and that miR-106b could suppress both.The blockage of MMP2 by RNA interference mimicked the anti-migration and anti-invasion effects of miR-106b, and introduction of MMP2 antagonized the function of miR-106b.

View Article: PubMed Central - PubMed

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.

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Effects of matrix metalloproteinase 2 (MMP2) on osteoclastogensis and removal of extracellular signal-regulated kinases (ERK) from tumor cells. (a) Western blot showing the level of ERK and p-ERK in the conditioned medium (CM) from SUM1315-bo cells. MiR-106b was shown to directly inhibit MMP2 and consequently decrease ERK and p-ERK expression. *P < 0.05. (b) Alteration of the RANKL/OPG abundance ratio in osteoblasts by MMP2 to favor osteoclast differentiation. RANKL and OPG were detected using immunoblotting in the culture media of HMSC-derived osteoblasts under different CM conditions. The RANKL/OPG ratio of the group of HMSC-derived osteoblasts cells (Os) (RANKL/OPG ratio = 0.28) and the group of HMSC-derived osteoblasts cultured using CM from MMP2 knockdown SUM1315-bo cells (MMP2i-Os) (RANKL/OPG ratio = 0.749) was significantly decreased when compared with the group of HMSC-derived osteoblasts cultured using CM from SUM1315 CM tumor cells (SUM1315-BO-Os) (RANKL/OPG ratio = 3.17). **P < 0.01.
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fig05: Effects of matrix metalloproteinase 2 (MMP2) on osteoclastogensis and removal of extracellular signal-regulated kinases (ERK) from tumor cells. (a) Western blot showing the level of ERK and p-ERK in the conditioned medium (CM) from SUM1315-bo cells. MiR-106b was shown to directly inhibit MMP2 and consequently decrease ERK and p-ERK expression. *P < 0.05. (b) Alteration of the RANKL/OPG abundance ratio in osteoblasts by MMP2 to favor osteoclast differentiation. RANKL and OPG were detected using immunoblotting in the culture media of HMSC-derived osteoblasts under different CM conditions. The RANKL/OPG ratio of the group of HMSC-derived osteoblasts cells (Os) (RANKL/OPG ratio = 0.28) and the group of HMSC-derived osteoblasts cultured using CM from MMP2 knockdown SUM1315-bo cells (MMP2i-Os) (RANKL/OPG ratio = 0.749) was significantly decreased when compared with the group of HMSC-derived osteoblasts cultured using CM from SUM1315 CM tumor cells (SUM1315-BO-Os) (RANKL/OPG ratio = 3.17). **P < 0.01.

Mentions: Because the MAPK pathway has been linked to the metastatic cascade,14 we hypothesized that MMP2 may regulate BC bone metastasis and may be associated with the components of the MAPK pathway. To test our hypothesis, we performed Western blot analysis for p-ERK and ERK protein in untransfected cells (N), miR-106b (106b), miR-106bI (106bI), or si-MMP2 and in cells overexpressing MMP2 (M–O). Cells treated with miR-106bI showed higher levels of the ratio p-ERK/ERK protein than controls (P < 0.01), while miR-106b and si-MMP2 cells expressed lower levels of the ratio p-ERK/ERK (P < 0.01) (Fig.5a). These data indicate that miR-106b's ability to decrease invasion and migration is attributable, in part, to its capacity to inhibit MMP2 and decrease the level of activated ERK expression.


Downregulation of miR-106b induced breast cancer cell invasion and motility in association with overexpression of matrix metalloproteinase 2.

Ni X, Xia T, Zhao Y, Zhou W, Wu N, Liu X, Ding Q, Zha X, Sha J, Wang S - Cancer Sci. (2013)

Effects of matrix metalloproteinase 2 (MMP2) on osteoclastogensis and removal of extracellular signal-regulated kinases (ERK) from tumor cells. (a) Western blot showing the level of ERK and p-ERK in the conditioned medium (CM) from SUM1315-bo cells. MiR-106b was shown to directly inhibit MMP2 and consequently decrease ERK and p-ERK expression. *P < 0.05. (b) Alteration of the RANKL/OPG abundance ratio in osteoblasts by MMP2 to favor osteoclast differentiation. RANKL and OPG were detected using immunoblotting in the culture media of HMSC-derived osteoblasts under different CM conditions. The RANKL/OPG ratio of the group of HMSC-derived osteoblasts cells (Os) (RANKL/OPG ratio = 0.28) and the group of HMSC-derived osteoblasts cultured using CM from MMP2 knockdown SUM1315-bo cells (MMP2i-Os) (RANKL/OPG ratio = 0.749) was significantly decreased when compared with the group of HMSC-derived osteoblasts cultured using CM from SUM1315 CM tumor cells (SUM1315-BO-Os) (RANKL/OPG ratio = 3.17). **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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fig05: Effects of matrix metalloproteinase 2 (MMP2) on osteoclastogensis and removal of extracellular signal-regulated kinases (ERK) from tumor cells. (a) Western blot showing the level of ERK and p-ERK in the conditioned medium (CM) from SUM1315-bo cells. MiR-106b was shown to directly inhibit MMP2 and consequently decrease ERK and p-ERK expression. *P < 0.05. (b) Alteration of the RANKL/OPG abundance ratio in osteoblasts by MMP2 to favor osteoclast differentiation. RANKL and OPG were detected using immunoblotting in the culture media of HMSC-derived osteoblasts under different CM conditions. The RANKL/OPG ratio of the group of HMSC-derived osteoblasts cells (Os) (RANKL/OPG ratio = 0.28) and the group of HMSC-derived osteoblasts cultured using CM from MMP2 knockdown SUM1315-bo cells (MMP2i-Os) (RANKL/OPG ratio = 0.749) was significantly decreased when compared with the group of HMSC-derived osteoblasts cultured using CM from SUM1315 CM tumor cells (SUM1315-BO-Os) (RANKL/OPG ratio = 3.17). **P < 0.01.
Mentions: Because the MAPK pathway has been linked to the metastatic cascade,14 we hypothesized that MMP2 may regulate BC bone metastasis and may be associated with the components of the MAPK pathway. To test our hypothesis, we performed Western blot analysis for p-ERK and ERK protein in untransfected cells (N), miR-106b (106b), miR-106bI (106bI), or si-MMP2 and in cells overexpressing MMP2 (M–O). Cells treated with miR-106bI showed higher levels of the ratio p-ERK/ERK protein than controls (P < 0.01), while miR-106b and si-MMP2 cells expressed lower levels of the ratio p-ERK/ERK (P < 0.01) (Fig.5a). These data indicate that miR-106b's ability to decrease invasion and migration is attributable, in part, to its capacity to inhibit MMP2 and decrease the level of activated ERK expression.

Bottom Line: MMP2 was shown to be a direct target of miR-106b.Both gain- and loss-of-function studies showed that MMP2 could promote the migration and invasion of BC cells and that miR-106b could suppress both.The blockage of MMP2 by RNA interference mimicked the anti-migration and anti-invasion effects of miR-106b, and introduction of MMP2 antagonized the function of miR-106b.

View Article: PubMed Central - PubMed

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
Related in: MedlinePlus