Regulation of Breast Cancer and Bone Metastasis by MicroRNAs

Figure 1

Biogenesis and function of microRNAs. RNA polymerase 2/3 binds to the promoter region of specific DNA sequence and forms a hair pin structure of the pri-miRNA. DGCR8 (Pasha) associates with protein Drosha which process pri-miRNA to pre-miRNA (by cleaving nucleotides from hair pin). Pre-miRNA is exported into cytoplasm with shuttle protein exportin. In mammals, the pre-miRNA is loaded onto a multiprotein complex consisting minimally of Dicer, Tar RNA Binding Protein (TRBP), and Ago2. The RNase III enzyme Dicer processes the precursor by cleaving the stem loop to produce the mature miRNA (canonical pathway) [11–13]. The precursor can be loaded directly onto Ago2 protein, and this Argonaute cleaves the precursor RNA of this miRNA [13]. The 5′ nucleotide of the miRNA guide strand, especially 5′ U, functions as an additive anchor and helps Ago proteins to load mismatch-containing miRNA/miRNA duplexes [14]. Of the two strands the guide strand is integrated with RISC forming miRNA-RISC complex, and other strand is degraded [13–16]. RISC is involved in inhibition of translation initiation, inhibition of translation elongation, or mRNA deadenylation [15–17].