title: Regulatory interplay between miR-21, JAG1 and 17beta-estradiol (E2) in breast cancer cells.
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.
authors.affiliation: Genetics and Biotechnology Lab, Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Ireland.
authors.forename: S Duygu
authors.initials: SD
authors.lastname: Selcuklu
authors.forename: Mark T A
authors.initials: MT
authors.lastname: Donoghue
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kerin
authors.forename: Charles
authors.initials: C
authors.lastname: Spillane
mesh_terms: D020413:3' Untranslated Regions; D001943:Breast Neoplasms / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D000072099:Serrate-Jagged Proteins
chemical_list: D020413:3' Untranslated Regions; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; C524940:MIRN21 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D000072099:Serrate-Jagged Proteins; D004958:Estradiol