Abstract
Estrogen Receptor β (ERβ) exerts oncosuppressive functions in breast cancer (BC) also in the absence of physiological ligands. Ligand‐independent actions of ERβ were investigated by expressing it in MCF‐7 and ZR75.1 BC cells. Interaction proteomics revealed >300 nuclear interacting partners, comprising proteins involved in transcriptional gene silencing by miRNAs. miRNA profiling (smallRNA‐Seq) and quantitative proteomics (iTRAQ) of ligand‐free ERβ+ vs ERβ‐ BC cells showed >100 miRNAs and >700 proteins whose expression is modulated by ERβ. Interestingly, these results combined with transcriptome analysis revealed post‐transcriptional regulation of protein expression by unliganded ERβ mediated by miRNAs. Forced expression of a mimic of ERβ‐responsive miR‐30a‐5p led to the identification of several transcripts targeted by this small RNA in BC cells, including 11 encoding regulatory proteins whose intracellular concentration was strongly affected by unliganded ERβ. These results suggest that regulation of BC cell functions by ligand‐free ERβ via miRNAs may exert a key role in the control of the biological and clinical phenotype of BC.Grant Funding Source: Supported by: FIRC (fellowship to GN) and AIRC (Grant IG‐13176 to AW and fellowship to MR)
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