Micro RNAs (
miRNAs) are small non-coding RNAs which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In
breast cancer, expression of
miRNAs is frequently dysregulated. Both
tumor suppressor activity and oncogenic properties have been assigned to specific
miRNAs, which modulate virtually all relevant stages of
breast cancer progression, including
tumor cell proliferation, apoptosis resistance,
cancer cell migration, invasiveness and
metastasis,
tumor angiogenesis and cancer stem cell self-renewal.
miRNA expression has been studied by microarray profiling, bead-based technologies and quantitative real-time PCR in archived
formalin-fixed
paraffin-embedded
tumor specimens as well as blood and serum samples, allowing to identify specific
miRNAs as novel diagnostic, prognostic and predictive markers. Moreover, the investigation of single nucleotide polymorphisms both in putative
miRNA binding sites in the
3'UTRs of target genes, as well as in
miRNA-endocing genes have revealed their diagnostic potential. In vitro experiments employing established
breast cancer cell lines and in vivo xenograft studies have demonstrated the efficacy of
oligonucleotide-based overexpression and inhibitor approaches of
miRNA-targeted
experimental therapies. Numerous studies have identified specific targets of
miRNA action in
breast cancer, including the established markers Her2/neu and
ERalpha, TP53, and markers of angiogenesis. The future application of
locked-nucleic acid miRNA inhibitors, and synergistic approaches involving conventional
breast cancer therapeutics opens up promising new perspectives in
breast cancer therapy.