ABSTRACT
Overview ................................................................................................................ 352 19.1 Introduction .................................................................................................. 352 19.2 miRNAs: Tiny RNAs That Regulate Gene Expression ............................... 352
19.2.1 Biogenesis ......................................................................................... 352 19.2.2 Molecular Mechanisms of Gene Silencing ....................................... 353 19.2.3 Combinatorial Gene Regulation ....................................................... 355
19.3 Aberrant Expression of miRNAs and the Development of Cancer .............. 356 19.3.1 Aberrations at the Chromosomal Level ............................................ 358 19.3.2 Defects in microRNA Biogenesis Pathway ...................................... 361
19.3.2.1 Drosha Processing ............................................................. 361 19.3.2.2 Dicer Processing ................................................................ 362 19.3.2.3 miRNA Targeting .............................................................. 363
19.4 Unique miRNA Profiles in Specific Cancer Types ...................................... 363 19.5 OncoMiRs: Playing a Direct Role in Oncogenesis ....................................... 365
19.5.1 miR-17-92 Multicistron .....................................................................366 19.5.2 miR-155 ............................................................................................. 368 19.5.3 miR-21 .............................................................................................. 369
19.6 Oncogenic Pathways Controlled by Deregulated microRNAs ..................... 369 19.6.1 miRNAs and Proto-Oncogene c-myc ............................................... 370 19.6.2 miRNAs in the Oncogenic RAS Pathway ........................................ 373
19.7 miRNAs in Stem Cells and Extension to Cancer Stem Cells....................... 374 19.8 MicroRNAs and Hematopoiesis ................................................................... 378 19.9 Viral miRNAs............................................................................................... 381 19.10 Conclusions and Future Perspectives........................................................... 383 Acknowledgments ..................................................................................................384 References ..............................................................................................................384
