title: Luminal long non-coding RNAs regulated by estrogen receptor alpha in a ligand-independent manner show functional roles in breast cancer.
abstract: Estrogen Receptor alpha (ERα) activation by estrogenic hormones induces luminal breast cancer cell proliferation. However, ERα plays also important hormone-independent functions to maintain breast tumor cells epithelial phenotype. We reported previously by RNA-Seq that in MCF-7 cells in absence of hormones ERα down-regulation changes the expression of several genes linked to cellular development, representing a specific subset of estrogen-induced genes. Here, we report regulation of long non-coding RNAs from the same experimental settings. A list of 133 Apo-ERα-Regulated lncRNAs (AER-lncRNAs) was identified and extensively characterized using published data from cancer cell lines and tumor tissues, or experiments on MCF-7 cells. For several features, we ran validation using cell cultures or fresh tumor biopsies. AER-lncRNAs represent a specific subset, only marginally overlapping estrogen-induced transcripts, whose expression is largely restricted to luminal cells and which is able to perfectly classify breast tumor subtypes. The most abundant AER-lncRNA, DSCAM-AS1, is expressed in ERα+ breast carcinoma, but not in pre-neoplastic lesions, and correlates inversely with EMT markers. Down-regulation of DSCAM-AS1 recapitulated, in part, the effect of silencing ERα, i.e. growth arrest and induction of EMT markers. In conclusion, we report an ERα-dependent lncRNA set representing a novel luminal signature in breast cancer cells.
authors.affiliation: Center for Molecular Systems Biology, University of Turin, Turin, Italy.|Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Miano
authors.affiliation: Center for Molecular Systems Biology, University of Turin, Turin, Italy.|Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.|Department of Computer Science, University of Turin, Turin, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Ferrero
authors.affiliation: Center for Molecular Systems Biology, University of Turin, Turin, Italy.|Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.|Bioindustry Park Silvano Fumero, Turin, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Reineri
authors.affiliation: Center for Molecular Systems Biology, University of Turin, Turin, Italy.|Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Livia
authors.initials: L
authors.lastname: Caizzi
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Annaratone
authors.affiliation: Center for Molecular Systems Biology, University of Turin, Turin, Italy.|Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ricci
authors.affiliation: Center for Molecular Systems Biology, University of Turin, Turin, Italy.|Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Santina
authors.initials: S
authors.lastname: Cutrupi
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Castellano
authors.affiliation: Center for Molecular Systems Biology, University of Turin, Turin, Italy.|Department of Computer Science, University of Turin, Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cordero
authors.affiliation: Center for Molecular Systems Biology, University of Turin, Turin, Italy.|Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: De Bortoli
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation; D004789:Enzyme Activation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D008024:Ligands; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering
keywords: DSCAM-AS1; breast cancer; data integration; estrogen receptor; lncRNA