Biology Reference
In-Depth Information
Like in eukaryote species, viral miRNAs stem from larger miRNA
precursors which are cleaved by the host's miRNA processing
machinery [ 20 ]. So far, miRNAs have only been detected in DNA
viruses, probably since a Drosha-mediated excision of a pri-miRNA
would lead to a cleavage of an RNA-genome.
In contrast, viruses not only use their own miRNAs but can also
interact with miRNAs of the host. Accordingly, it has been shown
that hepatitis C virus (HCV) replication essentially depends on a
host's cellular miRNA [ 23 ], which makes liver-specifi c miR-122 a
potential drug target against HCV infections (see below). Although
human miR-122 is not a disease-causing factor, it is essential in
HCV infection and thus appears to be a promising drug target.
4
Diagnostic Tool: miRNA Profi ling
Numerous reports describe association between altered miRNA
expression levels and human disease, irrespective of whether these
alterations are the cause for disease formation or just refl ect a patho-
logical condition. Despite the urge to fi nd the actual active mole-
cules that are targeted by mature miRNAs, recent fi ndings emphasize
that miRNA expression profi ling can already serve as a diagnostic
tool and this is at least the starting point for good cancer therapy.
Indeed, miRNA levels match certain expression patterns individu-
ally composed for many different types of cancer. Therefore, miRNA
profi ling as a diagnostic and prognostic tool has become valuable
especially in diagnosing tumor types that cannot be identifi ed with
biopsy samples on the basis of histological diagnosis alone.
Metastatic CUP is characterized by lack of primary tumor. In
chronic lymphocytic leukemia miRNA expression signature of 13
genes is associated with prognostic factor ZAP-70, a predictor of
early disease progression [ 24 ]. Expression signature differentiates
between leukemia with low and high ZAP-70 expression levels and
allows the prediction whether there will be disease progression or
not. miRNAs may be useful prognostic and diagnostic markers in
lung adenocarcinomas, because miRNA signatures differ with
tumor histology [ 25 ]. Additionally, high miR-155 and low miR-let-
7a expression showed correlation with poor outcome. Another
example of miRNA as a prognostic marker is the correlation of
miRNA expression with specifi c pathologic factors in breast cancer
[ 26 ]. Among 29 differentially expressed miRNAs, miR-125b, miR-
145, miR-21, and miR-155 were most consistently deregulated in
cancer tissue. Comparison of various pathologic features, such as
estrogen and progesterone receptor expression and tumor stage,
with miRNA expression levels indicated a small number of differen-
tially expressed miRNAs according to specifi c breast cancer type.
Many more correlations between aberrant miRNA profi les and
human disease exist and have been extensively reviewed [ 27 , 28 ].
Search WWH ::




Custom Search