1. Regulatory interplay between miR-21, JAG1 and 17beta-estradiol (E2) in breast cancer cells.
- Author
-
Selcuklu SD, Donoghue MT, Kerin MJ, and Spillane C
- Subjects
- 3' Untranslated Regions, Cell Line, Tumor, Down-Regulation, Estradiol pharmacology, Female, Humans, Jagged-1 Protein, MicroRNAs genetics, Promoter Regions, Genetic drug effects, Promoter Regions, Genetic genetics, Serrate-Jagged Proteins, Breast Neoplasms metabolism, Calcium-Binding Proteins metabolism, Estradiol metabolism, Intercellular Signaling Peptides and Proteins metabolism, Membrane Proteins metabolism, MicroRNAs metabolism
- Abstract
Overexpression of the oncomir miR-21 is associated with many cancers, including breast cancer. Elevated levels of Jagged-1 (JAG1), a predicted miR-21 target, are implicated in estrogen receptor negative (ER-) breast cancer. We demonstrate (by ablation of the miR-21 binding site in the JAG1 3'UTR) that miR-21 directly targets and represses JAG1 levels in MCF-7 (ER+) breast cancer cells. MiR-21 targeting of JAG1 in MDA-MB-231 (ER-) breast cancer cells is dependent on miR-21 dosage (levels). In both cell lines, miR-21 and JAG1 expression levels were negatively correlated due to their regulatory relationship. In addition, 17beta-estradiol (E2) increases JAG1 levels by limiting (via downregulating miR-21 levels) the repressive effects of miR-21 on the JAG1 3'UTR. Our results reveal a regulatory interplay between miR-21, JAG1 and E2 that is important for advancing understanding of how the oncogenic potential of miR-21 and JAG1 manifests in different sub-types of breast cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF