MiRNA in bladder carcinogenesis: A review

Figure 1 Genetic carcinogenic pathways of bladder urothelial carcinomas incorporating micro RNA. FGFR3: Fibroblastic growth factor receptor 3.

Figure 2 Micro RNA biogenesis in human cells. After transcription by RNA polymerase II, the primary micro RNA (miRNA) precursor (Pri-miRNA) is cleaved by Drosha microprocessor complex and converted in Pre-miRNA, a 60-70 nt double-strand molecule. The Pre-miRNA is transported from nucleus to the cytoplasm by Exportin-5 and then it is cleaved by Dicer to generate the miRNA duplex. Again, Dicer enzyme acts over miRNA duplex and produces single-strand mature miRNA that, in turn, is incorporated into RNA-Induced Silencing Complex (RISC). RISC drivers mature miRNA to the target messenger RNA (mRNA), triggering mRNA cleavage (Slicer activity) or inhibition of translation by complete or incomplete complementarity, respectively.

Figure 3 MiR-100 in low-grade non-invasive urothelial carcinoma carcinogenesis. Under-expression of miR-100 leads to FGFR3 gene over-expression, stimulus to PI3K/AKT/STAT pathway and low-grade non-invasive tumor development. Adapted by Wu[19], 2009. FGFR3: Fibroblastic growth factor receptor 3; UC: Urothelial carcinoma.

Figure 4 MiR-100 and miR-21 in high-grade invasive urothelial carcinoma carcinogenesis. High levels of miR-100 inhibit retinoblastoma (RB1) and over-expression of miR-21 suppresses p53 and phosphatase and tensin homolog gene (PTEN), three crucial protective genes. Inactivity of RB1 associated with loss of function of p53 and PTEN trigger high-grade urothelial carcinoma (UC) carcinogenesis. Adapted by Wu[19], 2009.