MicroRNA Maturation and Human Disease - miRNA Maturation: Methods and Protocols - page 13

mechanisms of miRNA function but also with the perspective to
affect human disease formation and progression [ 16 ]. As the expres-
sion pattern of certain miRNAs correlates with a variety of human
diseases like cancer, effort is directed towards acquisition of simple
and reliable methods to map miRNA expression profi les. In order
to specifi cally recognize the “signature” of for example cancerogen-
esis, several approaches to control miRNA function by manipulat-
ing its formation or its maturation have been described [ 17 ].

2 miRNAs in Human Disease

Given the importance of miRNAs for gene regulation especially in
the context of developmental processes and keeping in mind the
high number of ~1,500 known human miRNAs, the discovery of
possible roles for miRNAs in human pathology is not surprising.
Early research into that direction was directed towards the expres-
sion levels of miRNAs in diseases characterized by a lack of diagnos-
tic tools, especially in cancer. For example, metastatic cancer of
unknown primary site (CUP) is characterized by lack of primary
tumors. Lu et al. analyzed 17 poorly differentiated tumors by using
a training set of about 70 more differentiated tumors belonging to
11 different types as a classifi er based on available miRNA profi les
[ 18 ]. Surprisingly, the accuracy of diagnoses based on 217 miRNAs
was higher as compared to a set of 16,000 mRNAs. This and similar
studies initiated a tremendous effort in the investigation of the role
of miRNA in human disease. In general, it can be stated that there
are different kinds of links between miRNA and human disease,
which include (a) miRNAs of viral origins, (b) miRNAs as biomark-
ers that only refl ect disease states, (c) miRNAs with individual roles
as triggers or suppressors of disease development, and (d) alterations
in the miRNA processing machinery that may affect the expression
of many if not all miRNAs. Lastly, we will point out novel lines of
research aimed at gaining control over miRNA-mediated disease.

3 Viral miRNAs

Some disease-related miRNAs are not of human origin but are
encoded by viruses [ 19 ]. Virus-encoded miRNAs have been shown
to directly downregulate factors of the host's immune system [ 20 ].
In addition, viruses have also evolved the ability to downregulate
or upregulate the expression of specifi c cellular miRNAs to enhance
their replication. Some viruses gain control over cellular processes
by mimicking the host's miRNAs [ 21 ], while other virus-encoded
miRNAs are directed against the viral mRNAs [ 19 ]. The signifi cance
of viral miRNAs is impressively highlighted by the fact that viral
miRNAs can be critical for host cell transformation in vivo [ 22 ].