ABSTRACT
The number of mature microRNAs (miRNAs) in the human genome is estimated to be around several hundred. This small group of molecules has a major impact on gene regulatory networks because they can target a thousand overlapping messenger RNAs (mRNAs), or roughly onethird of all human mRNAs. The degradation or translational suppression of mRNAs is induced based on the degree of complementarity between an miRNA and its target mRNAs (Table 19.1). Research on miRNAs, which compose small noncoding fragments of RNA, has focused on the unique roles of these molecules in tumorigenesis in humans, although the importance of miRNAs,
19.1 Introduction .......................................................................................................................... 359 19.2 miRNA Signatures in Tumors .............................................................................................. 361
19.2.1 Colorectal and Gastric Cancers ................................................................................ 362 19.2.2 Hepatocellular Carcinomas ...................................................................................... 363 19.2.3 Lung Cancers ............................................................................................................ 363 19.2.4 Breast Cancers .......................................................................................................... 363 19.2.5 Brain Tumors ............................................................................................................364 19.2.6 Hematological Tumors ..............................................................................................364 19.2.7 Urinary Tumors ........................................................................................................ 365 19.2.8 Genital Tumors ......................................................................................................... 365 19.2.9 Endocrine Tumors.....................................................................................................366
19.3 Important Reminder .............................................................................................................366 19.4 Perspectives .......................................................................................................................... 367 19.5 Conclusions ........................................................................................................................... 368 Acknowledgments .......................................................................................................................... 369 References ...................................................................................................................................... 369
specišcally lin-4 and let-7 encoding 22-and 21-nucleotide RNAs, respectively, was originally implicated in the timing of stem cell division and differentiation in the nematode Caenorhabditis elegans (Lagos-Quintana et al., 2001; Lau et al., 2001; Lee and Ambros, 2001). Subsequently, let-7 has been shown to act as a tumor suppressor, because the down-regulation of let-7 resulted in a tumor-prone phenotype, a less-differentiated state of cancer cells, and a poor prognosis of tumor patients (Büssing et al., 2008; Jérôme et al., 2007; Shell et al., 2007). The šnding that the mir-1792 cluster is upregulated in B cell lymphoma, compared with normal tissue, strongly suggesting that miRNA may be a potential human oncogene (He et al., 2005). A relationship between miRNA and cancer has also been suggested by the fact that about half of the miRNA genes are located in cancer-associated genomic regions or in fragile sites of the genome, and several miRNAs located in deleted regions have been shown to be down-regulated in cancer samples (Calin et al., 2004). Accumulating evidence supports the notion that miRNAs have critical roles that contribute to tumor formation including onset, progression, invasion, migration, and metastasis as oncogenes or tumor-suppressor genes (Table 19.2), and miRNAs are expected to be useful as biomarkers for the diagnosis, prognosis, and treatment of cancer in the near future (Ahmed, 2007; Bandres et al., 2007; Baranwal and Alahari, 2010; Barbarotto et al., 2008; Bartels and Tsongalis, 2009; Blenkiron and Miska, 2007; Calin and Croce, 2006a, 2006b; Croce, 2009; Cummins and Velculescu, 2006; Deng et al., 2008; Dillhoff et al., 2009; Drakaki and Iliopoulos, 2009; Esquela-Kerscher and Slack, 2006; Fabbri et al., 2008; Garzon et al., 2006, 2009; Gusev and Brackett, 2007; Hagan and Croce, 2007; Hammond, 2006; Hernando, 2007; Hwang and Mendell, 2007; Iorio and Croce, 2009; Jay et al., 2007; Kent and Mendell, 2006; Lee and Dutta, 2006, 2009; Lotterman et al., 2008; Lu et al.,
