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MiR-155 is a liposarcoma oncogene that targets casein kinase-1α and enhances β-catenin signaling.
[dedifferentiated liposarcoma]
Liposarcoma
can
be
an
aggressive
,
debilitating
,
and
fatal
malignancy
.
In
this
study
,
we
identifed
miRNAs
associated
with
the
differentiation
status
of
liposarcoma
to
gain
insight
into
the
basis
for
its
progression
.
miRNA
expression
profiles
determined
in
human
tumors
and
normal
fat
specimens
identified
a
dedifferentiated
tumor
expression
signature
consisting
of
35
miRNAs
.
Deregulated
miRNA
expression
was
confirmed
in
a
second
independent
sample
cohort
.
The
miR-
155
was
the
most
overexpressed
miRNA
and
functional
investigations
assigned
an
important
role
in
the
growth
of
dedifferentiated
liposarcoma
cell
lines
.
Transient
or
stable
knockdown
of
miR-
155
retarded
tumor
cell
growth
,
decreased
colony
formation
,
and
induced
G
(
1
)
-
S
cell-cycle
arrest
in
vitro
and
blocked
tumor
growth
in
murine
xenografts
in
vivo
.
We
identified
casein
kinase
1
α
(
CK
1
α
)
as
a
direct
target
of
miR-
155
control
which
enhanced
β-catenin
signaling
and
cyclin
D
1
expression
,
promoting
tumor
cell
growth
.
In
summary
,
our
results
point
to
important
functions
for
miR-
155
and
β-catenin
signaling
in
progression
of
liposarcoma
,
revealing
mechanistic
vulnerabilities
that
might
be
exploited
for
both
prognostic
and
therapeutic
purposes
.
Diseases
Validation
Diseases presenting
"revealing mechanistic vulnerabilities that might be exploited for both prognostic and therapeutic purposes"
symptom
dedifferentiated liposarcoma
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