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.
Highlights
Breast cancer (BC) is a common malignant tumor in women worldwide [1]
The transforming growth factor β (TGFβ) superfamily receptor signaling pathway plays a key role in the tumorigenesis of BC [2,3,4,5], in which action of TGFβ receptor signaling by its ligand transforming growth factor β 1 (TGFβ1) promotes a biological process called EpithelialMesenchymal Transition, which cancer cells use to favor an invasive and metastatic phenotype (EMT) [6,7,8,9]
We recently reported that Bone morphogenetic protein-7 (BMP7) does not modify TGFβ1stimulated phosphorylation of the TGFβ receptor, but significantly inhibited activation of epithelialmesenchymal transition (EMT)-related genes by TGFβ1 in BC cells, thereby reducing TGFβ1mediated cell growth and metastasis [16]
Summary
The transforming growth factor β (TGFβ) superfamily receptor signaling pathway plays a key role in the tumorigenesis of BC [2,3,4,5], in which action of TGFβ receptor signaling by its ligand TGFβ1 promotes a biological process called EpithelialMesenchymal Transition, which cancer cells use to favor an invasive and metastatic phenotype (EMT) [6,7,8,9]. In this process, cancer cells begin to secrete proteinases in order to traverse collagenous extracellular matrix proteins.
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