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MicroRNAs (miRNAs) are a new class of non-protein-coding,
endogenous, small RNAs typically 21-23 nucleotide (nt) in
length, evolutionarily conserved in many organisms as disparate
as yeast, fruit flies, human and plants (Bartel, 2004).
They play profound and pervasive roles in manipulating genes
involved in development, proliferation, apoptosis and stress
response in various eukaryotes (Ambros, 2004). Recent evidences
demonstrate that aberrant miRNA expression is a hallmark
of tumor development, revealing that miRNA genes could function
as potential oncogenes and repressors in the human body
(He et al., 2005b; and Volinia et al., 2006).
Ever since the first miRNA was discovered in Caenorhabditis
elegans, this group of tiny RNAs has moved to the forefront
of biology (Lee et al., 1993; and Wightman et al., 1993).
Zhang (2008) coined the term "microRNomics" to
describe the newly emerging subdiscipline of genomics that
studies the identification, expression, biogenesis, structure
and regulation of expression, targets and biological functions
of miRNAs on the genomic scale. A number of studies show
that the abnormalities of the epigenome and microRNome are
interdependent. Till date around 600 miRNAs have been discovered,
and the estimated number of miRNA genes is as high as 1000
(http://microrna.sanger.ac.uk/Griffiths-Jones et al., 2008),
which constitute approximately 1-5% of the expressed genes.
Over half of miRNA genes (52.5%) are located in or near
fragile sites or cancer-associated genomic regions (Calin
et al., 2004b). miRNAs regulate the expression of more than
30% of protein-coding genes; currently, miRNAs are considered
to be one of the most important gene regulators. The initial
evidence for the involvement of miRNAs in cancers came from
a molecular study characterizing the 13q14 deletion in human
Chronic Lymphocytic Leukemia (CLL) (Calin et al., 2002).
Detailed deletion analysis indicated that these two miRNAs
are the only two genes within the small (30 kb) common region
which are lost in CLL patients, and expression analysis
indicated that either they were absent or downregulated
in a majority of CLL patients (Calin et al., 2002). MiRNA-mediated
regulation influences the normal development and function
of cells of the immune system, suggesting an additional
role for it in tumorigenesis (Kanellopoulou and Monticelli,
2008).
The strongest evidence supporting a causal role for miRNAs
in carcinogenesis comes from various genetic models in which
several miRNAs were shown to act as oncogenes (oncomirs)
(Esquela-Kerscher and Slack, 2006). Sequence-specific gene
silencing methods for both in vitro and in vivo target validation
have been developed and are being utilized by pharmaceutical
companies for prioritizing drug target candidates. Irrespective
of the actual role of the miRNAs in tumorigenesis, miRNA
expression profiles can also be valuable as diagnostic or
prognostic markers. In addition to cancer, RNAi provides
a new potential therapeutic tool applicable to a wide array
of disease targets.
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