@entity15073 inhibits endothelin A receptor and chemoresistance in XXXX .

@entity43 @entity1 @entity15073 @entity2232 @entity5 @entity900 @entity584 @entity902 @entity2231
UNASSIGNED: Drug resistance remains the major clinical barrier to successful treatment in @entity43 ( @entity43 ) @entity1 , and the evidence of microRNA involvement in drug resistance has been recently emerging. @entity2232 (ET-1)/ETA receptor ( @entity2231 ) axis is aberrantly activated in chemoresistant @entity43 cells and elicits pleiotropic effects promoting epithelial-to-mesenchymal transition (EMT) and the acquisition of chemoresistance. However, the relationship between @entity2231 and miRNA is still unknown. Hence, in this study we evaluated whether dysregulation of miRNA might enhance @entity2231 expression in sensitive and resistant @entity43 cells. Based on bioinformatic tools, we selected putative miRNA able to recognize the 3'UTR of @entity2231 . An inverse correlation was observed between the expression levels of @entity15073 and @entity2231 in both @entity43 cell lines and @entity5 samples. @entity15073 was found to specifically bind to the 3'UTR of @entity2231 mRNA, indicating that @entity2231 is a direct target of @entity15073 . Overexpression of @entity15073 decreased @entity584 and mitogen activated protein kinase signaling pathway activation, cell proliferation, invasion, plasticity, EMT marker levels, and vascular endothelial growth factor release. Interestingly, ectopic expression of @entity15073 re-sensitized @entity902 -resistant @entity43 cells to @entity900 -induced apoptosis. Consistently, resistant @entity43 xenografts overexpressing @entity15073 resulted in significantly less @entity5 growth than controls. Together our study provides a new perspective on the regulatory mechanism of @entity2231 gene. Interestingly, our findings highlight that blockade of @entity2231 regulatory axis is the mechanism underlying the @entity5 suppressor function of @entity15073 in chemoresistant @entity43 cells.
