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Luminal long non-coding RNAs regulated by estrogen receptor alpha in a ligand-independent manner show functional roles in breast cancer.
- Source :
-
Oncotarget [Oncotarget] 2016 Jan 19; Vol. 7 (3), pp. 3201-16. - Publication Year :
- 2016
-
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.
- Subjects :
- Biomarkers, Tumor genetics
Cell Line, Tumor
Cell Proliferation genetics
Cell Survival genetics
Down-Regulation
Enzyme Activation
Epithelial-Mesenchymal Transition genetics
Estrogens metabolism
Female
HEK293 Cells
Humans
Ligands
MCF-7 Cells
RNA Interference
RNA, Small Interfering genetics
Breast Neoplasms genetics
Breast Neoplasms pathology
Estrogen Receptor alpha genetics
Gene Expression Regulation, Neoplastic
RNA, Long Noncoding genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26621851
- Full Text :
- https://doi.org/10.18632/oncotarget.6420