Moreover, gene network analysis showed that SMAD7 expression is regulated by SETDB1 levels, indicating that up-regulation of SMAD7 by SETDB1 knockdown inhibited BRC metastasis.
The set of miRNAs hsa-mir-146a, hsa-mir-93, hsa-mir-375, hsa-mir-205, hsa-mir-15a, hsa-mir-21, hsa-mir-20a, hsa-mir-503, hsa-mir-29c, hsa-mir-497, hsa-mir-107, hsa-mir-125a, hsa-mir-200c, hsa-mir-212, hsa-mir-429, hsa-mir-34a, hsa-let-7c, hsa-mir-92b, hsa-mir-33a, hsa-mir-15b, hsa-mir-224, hsa-mir-185 and hsa-mir-10b integrate a profile that critically regulates the expression of the mRNA coding for Smad7 in breast cancer.
In the current investigation, we determined that loss of Merlin in breast cancer tissues is concordant with the loss of the inhibitory SMAD, SMAD7, of the TGF-β pathway.
Taken together, our results identified the proliferation promoting role of SMAD7 in breast cancer and therefore established the regulations of SMAD7 in breast cancer by miR-497 through a posttranscriptional mechanism.
We therefore conclude that breast cancer cells require close contact with fibroblasts in order to upregulate Smad7 which, in turn, leads to decreased ERK signalling resulting in diminished expression of the stromal proteins CCN2 and type I collagen.