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MicroRNA-137 inhibits BMP7 to enhance the epithelial-mesenchymal transition of breast cancer cells

View Article: PubMed Central - PubMed

ABSTRACT

Bone morphogenetic protein-7 (BMP7) is known to antagonize transforming growth factor β 1 (TGFβ1)-mediated fibrosis through suppressing epithelial-mesenchymal transition (EMT). We recently reported that BMP7 also antagonizes the effects of TGFβ1 in breast cancer (BC) tumorigenesis-related EMT. Nevertheless, the control of BMP7 expression in BC remains ill-defined. Here, we detected significantly lower levels of BMP7 and significantly higher levels of microRNA-137 (miR-137) in the BC specimens, relative to paired adjacent non-tumor breast tissue. BMP7 and miR-137 levels were correlated inversely. Additionally, the high miR-137 levels in BC specimens were correlated with reduced patient survival. In vitro, overexpression of miR-137 significantly increased cell EMT and invasion, while depletion of miR-137 significantly decreased cell EMT and invasion in BC cells. The increases in BC cell invasiveness by miR-137 appeared to result from its suppression of BMP7, through direct binding of miR-137 to the 3'-UTR of BMP7 mRNA, thereby blocking its protein translation in BC cells. This study sheds light on miR-137 as a crucial factor that enhances BC cell EMT and invasiveness, and points to miR-137 as a promising innovative therapeutic target for BC treatment.

No MeSH data available.


High miR-137 levels in BC specimens is associated with poor prognosisA-C. The levels of BMP7 and miR-137 in 40 pairs of BC tissues and adjacent non-tumor breast tissues (NT) were measured by Western blot (A) and RT-qPCR (B). C. A correlation test was performed between BMP7 and miR-137, using the 40 BC specimens. D. The 40 BC patients were followed-up for 60 months. The median value of all 40 cases was chosen as the cutoff point for separating miR-137-high cases (n=20) from miR-137-low cases (n=20). Kaplan-Meier curves were performed to compare 5-year survival between two groups. *p<0.05. **p<0.01. N=40.
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Figure 1: High miR-137 levels in BC specimens is associated with poor prognosisA-C. The levels of BMP7 and miR-137 in 40 pairs of BC tissues and adjacent non-tumor breast tissues (NT) were measured by Western blot (A) and RT-qPCR (B). C. A correlation test was performed between BMP7 and miR-137, using the 40 BC specimens. D. The 40 BC patients were followed-up for 60 months. The median value of all 40 cases was chosen as the cutoff point for separating miR-137-high cases (n=20) from miR-137-low cases (n=20). Kaplan-Meier curves were performed to compare 5-year survival between two groups. *p<0.05. **p<0.01. N=40.

Mentions: The levels of BMP7 and miR-137 in 40 pairs of resected BC tissues (Stage IV) and adjacent non-tumor breast tissues (NT) were measured by Western blot and RT-qPCR, respectively (Table 1). BC specimens contained significantly lower levels of BMP7 (Figure 1A), and significantly higher levels of miR-137 (Figure 1B). We then performed a correlation test using these 40 BC specimens, and detected a strong inverse correlation between BMP7 and miR-137 (Figure 1C, ɤ=-0.72, p<0.0001, N=40), indicating a possible regulatory relationship between miR-137 and BMP7 in BC. These patients were followed up for 60 months to assess overall survival. The relationship of miR-137 or BMP7 levels and clinicopathological characteristics was evaluated using multivariate Cox regression analysis, showing that both were significantly associated with survival of the BC patients (Table 2). Next, the median value for miR-137 in these patients was used as the cutoff point for separating miR-137-high cases (n=20) from miR-137-low cases (n=20). Kaplan-Meier curves showed that patients with high miR-137 levels in BC tissue had a significantly lower 5-year survival than those with low miR-137 levels in BC tissue (Figure 1D). These data suggest that high miR-137 levels in BC specimens may be associated with reduced patient survival.


MicroRNA-137 inhibits BMP7 to enhance the epithelial-mesenchymal transition of breast cancer cells
High miR-137 levels in BC specimens is associated with poor prognosisA-C. The levels of BMP7 and miR-137 in 40 pairs of BC tissues and adjacent non-tumor breast tissues (NT) were measured by Western blot (A) and RT-qPCR (B). C. A correlation test was performed between BMP7 and miR-137, using the 40 BC specimens. D. The 40 BC patients were followed-up for 60 months. The median value of all 40 cases was chosen as the cutoff point for separating miR-137-high cases (n=20) from miR-137-low cases (n=20). Kaplan-Meier curves were performed to compare 5-year survival between two groups. *p<0.05. **p<0.01. N=40.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5392333&req=5

Figure 1: High miR-137 levels in BC specimens is associated with poor prognosisA-C. The levels of BMP7 and miR-137 in 40 pairs of BC tissues and adjacent non-tumor breast tissues (NT) were measured by Western blot (A) and RT-qPCR (B). C. A correlation test was performed between BMP7 and miR-137, using the 40 BC specimens. D. The 40 BC patients were followed-up for 60 months. The median value of all 40 cases was chosen as the cutoff point for separating miR-137-high cases (n=20) from miR-137-low cases (n=20). Kaplan-Meier curves were performed to compare 5-year survival between two groups. *p<0.05. **p<0.01. N=40.
Mentions: The levels of BMP7 and miR-137 in 40 pairs of resected BC tissues (Stage IV) and adjacent non-tumor breast tissues (NT) were measured by Western blot and RT-qPCR, respectively (Table 1). BC specimens contained significantly lower levels of BMP7 (Figure 1A), and significantly higher levels of miR-137 (Figure 1B). We then performed a correlation test using these 40 BC specimens, and detected a strong inverse correlation between BMP7 and miR-137 (Figure 1C, ɤ=-0.72, p<0.0001, N=40), indicating a possible regulatory relationship between miR-137 and BMP7 in BC. These patients were followed up for 60 months to assess overall survival. The relationship of miR-137 or BMP7 levels and clinicopathological characteristics was evaluated using multivariate Cox regression analysis, showing that both were significantly associated with survival of the BC patients (Table 2). Next, the median value for miR-137 in these patients was used as the cutoff point for separating miR-137-high cases (n=20) from miR-137-low cases (n=20). Kaplan-Meier curves showed that patients with high miR-137 levels in BC tissue had a significantly lower 5-year survival than those with low miR-137 levels in BC tissue (Figure 1D). These data suggest that high miR-137 levels in BC specimens may be associated with reduced patient survival.

View Article: PubMed Central - PubMed

ABSTRACT

Bone morphogenetic protein-7 (BMP7) is known to antagonize transforming growth factor &beta; 1 (TGF&beta;1)-mediated fibrosis through suppressing epithelial-mesenchymal transition (EMT). We recently reported that BMP7 also antagonizes the effects of TGF&beta;1 in breast cancer (BC) tumorigenesis-related EMT. Nevertheless, the control of BMP7 expression in BC remains ill-defined. Here, we detected significantly lower levels of BMP7 and significantly higher levels of microRNA-137 (miR-137) in the BC specimens, relative to paired adjacent non-tumor breast tissue. BMP7 and miR-137 levels were correlated inversely. Additionally, the high miR-137 levels in BC specimens were correlated with reduced patient survival. In vitro, overexpression of miR-137 significantly increased cell EMT and invasion, while depletion of miR-137 significantly decreased cell EMT and invasion in BC cells. The increases in BC cell invasiveness by miR-137 appeared to result from its suppression of BMP7, through direct binding of miR-137 to the 3'-UTR of BMP7 mRNA, thereby blocking its protein translation in BC cells. This study sheds light on miR-137 as a crucial factor that enhances BC cell EMT and invasiveness, and points to miR-137 as a promising innovative therapeutic target for BC treatment.

No MeSH data available.