Limits...
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

Schematic of the modelMiR-137 enhances BC cell EMT and invasion, through translational suppression of BMP7.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5392333&req=5

Figure 6: Schematic of the modelMiR-137 enhances BC cell EMT and invasion, through translational suppression of BMP7.

Mentions: In order to ascertain whether miR-137 promotes BC cell invasion through suppressing BMP7, we prepared plasmids for BMP7 overexpression (BMP7) and depletion (shBMP7). First, MCF7-miR-137 cells were further transfected with BMP7, which increased BMP7 mRNA (Figure 3A) and protein (Figure 3B) in these cells. Overexpression of BMP7 abrogated the promoting effects of miR-137 on the EMT and cell invasion in MCF7 cells (Figure 4B-4C), without affected cell growth (Figure 4A). Next, BT474-as-miR-137 was further transfected with shBMP7, resulting in decreases in BMP7 mRNA (Figure 3C) and protein (Figure 3D) in these cells. We found that the effects of as-miR-137 on BMP7 protein compromised the effects of shBMP7 on BMP7 protein, which explained the findings in BC cells transfected with both as-miR-137 and shBMP7. We found that BMP7 suppression abolished the inhibitory effects of as-miR-137 on EMT and cell invasion in BT474 cells (Figure 5B-5C), without affected cell growth (Figure 5A). Thus, miR-137 may enhance BC cell invasion by suppressing BMP7 (Figure 6).


MicroRNA-137 inhibits BMP7 to enhance the epithelial-mesenchymal transition of breast cancer cells
Schematic of the modelMiR-137 enhances BC cell EMT and invasion, through translational suppression of BMP7.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Schematic of the modelMiR-137 enhances BC cell EMT and invasion, through translational suppression of BMP7.
Mentions: In order to ascertain whether miR-137 promotes BC cell invasion through suppressing BMP7, we prepared plasmids for BMP7 overexpression (BMP7) and depletion (shBMP7). First, MCF7-miR-137 cells were further transfected with BMP7, which increased BMP7 mRNA (Figure 3A) and protein (Figure 3B) in these cells. Overexpression of BMP7 abrogated the promoting effects of miR-137 on the EMT and cell invasion in MCF7 cells (Figure 4B-4C), without affected cell growth (Figure 4A). Next, BT474-as-miR-137 was further transfected with shBMP7, resulting in decreases in BMP7 mRNA (Figure 3C) and protein (Figure 3D) in these cells. We found that the effects of as-miR-137 on BMP7 protein compromised the effects of shBMP7 on BMP7 protein, which explained the findings in BC cells transfected with both as-miR-137 and shBMP7. We found that BMP7 suppression abolished the inhibitory effects of as-miR-137 on EMT and cell invasion in BT474 cells (Figure 5B-5C), without affected cell growth (Figure 5A). Thus, miR-137 may enhance BC cell invasion by suppressing BMP7 (Figure 6).

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