Luminal Long Non-coding RNAs Regulated by Estrogen Receptor Alpha in a Ligand-independent Manner Show Functional Roles in Breast Cancer
Overview
Authors
Affiliations
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.
Tiwari P, Tripathi L Cancers (Basel). 2024; 16(16).
PMID: 39199690 PMC: 11352509. DOI: 10.3390/cancers16162920.
Hu S, Han X, Liu G, Wang S Front Endocrinol (Lausanne). 2024; 15:1415722.
PMID: 39015175 PMC: 11249743. DOI: 10.3389/fendo.2024.1415722.
Suba Z Cancers (Basel). 2024; 16(8).
PMID: 38672654 PMC: 11049279. DOI: 10.3390/cancers16081573.
Endocrine nuclear receptors and long non‑coding RNAs reciprocal regulation in cancer (Review).
Cantile M, Cerrone M, di Bonito M, Moccia P, Tracey M, Ferrara G Int J Oncol. 2023; 64(1).
PMID: 38038050 PMC: 10705039. DOI: 10.3892/ijo.2023.5595.
Melone V, Salvati A, Brusco N, Alexandrova E, DAgostino Y, Palumbo D Int J Mol Sci. 2023; 24(2).
PMID: 36674656 PMC: 9863308. DOI: 10.3390/ijms24021145.