Estrogen receptor beta as epigenetic mediator of miR-10b and miR-145 in mammary cancer.

摘要: Even though the role of estrogen receptor alpha (ERα) in modulation breast cancer cells' behavior is thoroughly studied, biological functions its isoform, ERβ, are less elucidated. The suppression ERβ aggressive ERα-negative MDA-MB-231 cells resulted inhibition epithelial to mesenchymal transition (EMT) and major changes basic functional properties expression levels certain matrix components cells. This arrest metastatic potential suggests contribution induction a more phenotype epigenetic alterations responsible for ability tumor metastasize. Here, we report first time that leads significant profiles specific microRNAs, including miR-10b, miR-200b miR-145. Growth MCF-7 estrogen-free medium has diverse impact on miRNA these cells, suggesting effect estradiol profile depending ER status Enhanced miR-10b or silencing miR-145 clearly revealed microRNAs can regulate properties, EMT program known be implicated aggressiveness. Our data strongly regulation Erk1/2 signaling shERβ thus affecting extracellular (ECM) composition, syndecan-1, proteolytic behavior, especially MMP2, MMP7 MMP9 subsequently aggressiveness Accordingly, significantly increased induced EMT. Moreover, important gene protein ECM mediators, such as HER2 several MMPs, whereas it phosphorylated kinases crucial this pathway. These novel results suggest cell composition caused by closely related miRNA-induced alterations. Targeting ERβ-regulated promising tool diagnosis pharmaceutical targeting cancer.