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Tumor suppressive miRNA-34a suppresses cell proliferation and tumor growth of glioma stem cells by targeting Akt and Wnt signaling pathways.
[severe combined immunodeficiency]
MiRNA-
34
a
is
considered
as
a
potential
prognostic
marker
for
glioma
,
as
studies
suggest
that
its
expression
negatively
correlates
with
patient
survival
in
grade
III
and
IV
glial
tumors
.
Here
,
we
show
that
expression
of
miR-
34
a
was
decreased
in
a
graded
manner
in
glioma
and
glioma
stem
cell-lines
as
compared
to
normal
brain
tissues
.
Ectopic
expression
of
miR-
34
a
in
glioma
stem
cell-lines
HNGC-
2
and
NSG-K
16
decreased
the
proliferative
and
migratory
potential
of
these
cells
,
induced
cell
cycle
arrest
and
caused
apoptosis
.
Notably
,
the
miR-
34
a
glioma
cells
formed
significantly
smaller
xenografts
in
immuno-
deficient
mice
as
compared
with
control
glioma
stem
cell-lines
.
Here
,
using
a
bioinformatics
approach
and
various
biological
assays
,
we
identify
Rictor
,
as
a
novel
target
for
miR-
34
a
in
glioma
stem
cells
.
Rictor
,
a
defining
component
of
mTORC
2
complex
,
is
involved
in
cell
survival
signaling
.
mTORC
2
lays
downstream
of
Akt
,
and
thus
is
a
direct
activator
of
Akt
.
Our
earlier
studies
have
elaborated
on
role
of
Rictor
in
glioma
invasion
(
Das
et
al
.
,
2011
)
.
Here
,
we
demonstrate
that
miR
34
a
over-expression
in
glioma
stem
cells
profoundly
decreased
levels
of
p
-
AKT
(
Ser
473
)
,
increased
GSK
-
3
β
levels
and
targeted
for
degradation
β-catenin
,
an
important
mediator
of
Wnt
signaling
pathway
.
This
led
to
diminished
levels
of
the
Wnt
effectors
cyclin
D
1
and
c-myc
.
Collectively
,
we
show
that
the
tumor
suppressive
function
of
miR-
34
a
in
glioblastoma
is
mediated
via
Rictor
,
which
through
its
effects
on
AKT
/
mTOR
pathway
and
Wnt
signaling
causes
pronounced
effects
on
glioma
malignancy
.
Diseases
Validation
Diseases presenting
"profoundly decreased levels"
symptom
severe combined immunodeficiency
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