title: Effects of oestrogen on microRNA expression in hormone-responsive breast cancer cells.
abstract: Oestrogen receptor alpha (ERα) is a ligand-dependent transcription factor that mediates oestrogen effects in hormone-responsive cells. Following oestrogenic activation, ERα directly regulates the transcription of target genes via DNA binding. MicroRNAs (miRNAs) represent a class of small noncoding RNAs that function as negative regulators of protein-coding gene expression. They are found aberrantly expressed or mutated in cancer, suggesting their crucial role as either oncogenes or tumour suppressor genes. Here, we analysed changes in miRNA expression in response to oestrogen in hormone-responsive breast cancer MCF-7 and ZR-75.1 cells by microarray-mediated expression profiling. This led to the identification of 172 miRNAs up- or down-regulated by ERα in response to 17β-oestradiol, of which 52 are similarly regulated by the hormone in the two cell models investigated. To identify mechanisms by which ERα exerts its effects on oestrogen-responsive miRNA genes, the oestrogen-dependent miRNA expression profiles were integrated with global in vivo ERα binding site mapping in the genome by ChIP-Seq. In addition, data from miRNA and messenger RNA (mRNA) expression profiles obtained under identical experimental conditions were compared to identify relevant miRNA target transcripts. Results show that miRNAs modulated by ERα represent a novel genomic pathway to impact oestrogen-dependent processes that affect hormone-responsive breast cancer cell behaviour. MiRNome analysis in tumour tissues from breast cancer patients confirmed a strong association between expression of these small RNAs and clinical outcome of the disease, although this appears to involve only marginally the oestrogen-regulated miRNAs identified in this study.
authors.affiliation: Laboratory of Molecular Medicine and Genomics, Faculty of Medicine and Surgery, University of Salerno, via S. Allende 1, 84081 Baronissi, Salerno, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ferraro
authors.forename: Maria
authors.initials: M
authors.lastname: Ravo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Nassa
authors.forename: Roberta
authors.initials: R
authors.lastname: Tarallo
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: De Filippo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giurato
authors.forename: Francesca
authors.initials: F
authors.lastname: Cirillo
authors.forename: Claudia
authors.initials: C
authors.lastname: Stellato
authors.forename: Silvana
authors.initials: S
authors.lastname: Silvestro
authors.forename: Concita
authors.initials: C
authors.lastname: Cantarella
authors.forename: Francesca
authors.initials: F
authors.lastname: Rizzo
authors.forename: Daniela
authors.initials: D
authors.lastname: Cimino
authors.forename: Olivier
authors.initials: O
authors.lastname: Friard
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Biglia
authors.forename: Michele
authors.initials: M
authors.lastname: De Bortoli
authors.forename: Luigi
authors.initials: L
authors.lastname: Cicatiello
authors.forename: Ernesto
authors.initials: E
authors.lastname: Nola
authors.forename: Alessandro
authors.initials: A
authors.lastname: Weisz
mesh_terms: D000328:Adult; D000368:Aged; D001665:Binding Sites / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020218:Response Elements
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D035683:MicroRNAs; D004958:Estradiol