MicroRNAs in breast cancer pathogenesis

Abstract

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.