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characterized by deviant expression levels of mature or precursor
miRNA or both of them. This means that abnormally expressed
miRNAs affect transcripts of essential protein-coding genes rele-
vant in tumorigenesis, just as E2F1 transcription factor is targeted
by the mir-17-92 cluster.
One theory focuses on the assumption that miRNAs expressed
in various forms of cancer are from the same pool of miRNAs, dif-
ferentially expressed compared to corresponding normal tissue but
with different signatures for each tumor or cancer type [
52
].
Volinia et al. compared six solid cancers and found miR-21 to be
overexpressed in all of them. Two others, miR-17-5p and miR-
191, were overexpressed in fi ve cancer types. The answer of why
same miRNAs occur abnormally expressed in tumors with differ-
ent embryological origin may be a shared signaling pathway altered
in many kinds of tumors. MiR-21, for example, is thought to
directly target PTEN, a tumor suppressor encoding a phosphatase
that inhibits growth or survival pathways, which suggests that
miR-21 is an antiapoptotic factor in different tumor types [
53
].
In case of miR-17-92 locus, investigations are heading towards
two different directions. In a MYC-overexpressing human B-cell
line, MYC-mediated cellular proliferation is inhibited by inhibition
of E2F1 that is down-regulated by miR-17-92 cluster [
49
].
Contrary to that tumor-suppressor activity, the same cluster acts as
a potential oncogene in B-cell lymphomas by MYC interaction and
disabling apoptosis [
50
]. Therefore, one second theory focuses
more on the fact that the same miRNA can take part in distinct
pathways depending on gene expression pattern and cell type,
hence having not necessarily same effects on cell survival, growth,
and proliferation [
47
]. Giving defi nitive answers is diffi cult, because
the active molecules that are target of concerning miRNAs can
hardly be identifi ed while the state of precursor miRNA expression
can. RNA-binding proteins that are abnormally expressed in all
cancer types are suspected to be potential interaction partners of
miRNA [
47
,
54
].
6
Alterations in the miRNA Processing Machinery
Another theory concerns aberrancies in miRNA-processing genes
and proteins. miRNA expression should strongly correlate with
alterations of involved proteins. In a study on lung cancer Karube
et al. showed that expression levels of Dicer but not Drosha were
reduced, leading to a poor chance of survival [
55
]. Similar reduced
survival rates in relation to low Dicer amounts could be identifi ed
for let-7 miRNA [
56
]. Once again, these fi ndings suggest that
abnormalities in mature miRNA levels in cancer tissue emerge
from aberrant expression as well as aberrant miRNA maturation
process. Another study examined expression profi les of Drosha and
