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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.


Related in: MedlinePlus

Overexpression of miR-137 increases MCF7 EMT and cell invasion through suppressing BMP7A-C. MCF7 cell invasion by miR-137 overexpression (and BMP7 overexpression) in a transwell cell invasion assay, shown by quantification (A-B), and by representative images (C). *p<0.05. N=5.
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Figure 4: Overexpression of miR-137 increases MCF7 EMT and cell invasion through suppressing BMP7A-C. MCF7 cell invasion by miR-137 overexpression (and BMP7 overexpression) in a transwell cell invasion assay, shown by quantification (A-B), and by representative images (C). *p<0.05. N=5.

Mentions: The effects of miR-137 modification on the EMT and invasion of cultured BC cells were then investigated. We found that miR-137 overexpression in MCF7 cells did not alter cell growth in an MTT assay (Figure 4A), but significantly increased the potential of EMT and cell invasion in a transwell cell migration assay (Figure 4B-4C). Moreover, miR-137 depletion in BT474 cells did not alter cell growth in an MTT assay (Figure 5A), but significantly decreased the potential of EMT and cell invasion in a transwell cell migration assay (Figure 5B-5C). Thus, MiR-137 decreases BC cell EMT and invasion.


MicroRNA-137 inhibits BMP7 to enhance the epithelial-mesenchymal transition of breast cancer cells
Overexpression of miR-137 increases MCF7 EMT and cell invasion through suppressing BMP7A-C. MCF7 cell invasion by miR-137 overexpression (and BMP7 overexpression) in a transwell cell invasion assay, shown by quantification (A-B), and by representative images (C). *p<0.05. N=5.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Overexpression of miR-137 increases MCF7 EMT and cell invasion through suppressing BMP7A-C. MCF7 cell invasion by miR-137 overexpression (and BMP7 overexpression) in a transwell cell invasion assay, shown by quantification (A-B), and by representative images (C). *p<0.05. N=5.
Mentions: The effects of miR-137 modification on the EMT and invasion of cultured BC cells were then investigated. We found that miR-137 overexpression in MCF7 cells did not alter cell growth in an MTT assay (Figure 4A), but significantly increased the potential of EMT and cell invasion in a transwell cell migration assay (Figure 4B-4C). Moreover, miR-137 depletion in BT474 cells did not alter cell growth in an MTT assay (Figure 5A), but significantly decreased the potential of EMT and cell invasion in a transwell cell migration assay (Figure 5B-5C). Thus, MiR-137 decreases BC cell EMT and invasion.

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.


Related in: MedlinePlus