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Transcription factor OCT4 promotes cell cycle progression by regulating CCND1 expression in esophageal carcinoma.
[esophageal carcinoma]
The
CCND
1
gene
is
overexpressed
in
esophageal
cancer
and
accelerates
cell
cycle
progression
.
However
,
the
mechanism
whereby
the
upstream
genes
or
factors
directly
regulate
CCND
1
expression
remains
unknown
.
By
analyzing
the
5
'
-
UTR
region
of
the
CCND
1
gene
,
we
found
that
this
region
contains
an
octamer
motif
(
ATTTTGCAT
)
,
which
suggests
that
the
expression
of
CCND
1
might
be
directly
associated
with
octamer-binding
transcription
factor
4
(
OCT
4
)
.
In
this
study
,
the
wild-
type
and
the
octamer
motif-mutanted
CCND
1
promoters
were
cloned
,
and
their
corresponding
luciferase
reporter
vectors
were
then
constructed
to
study
the
molecular
mechanism
by
which
OCT
4
regulates
the
expression
of
CCND
1
and
influences
the
biological
behaviors
of
esophageal
cancer
cells
.
The
results
indicated
that
suppressing
the
expression
of
CCND
1
and
OCT
4
in
esophageal
cancer
cells
reduced
cell
proliferative
and
invasive
abilities
,
induced
cell
cycle
G
1
-
phase
arrest
,
and
slowed
the
growth
of
xenografts
in
nude
mice
.
Suppression
of
OCT
4
expression
significantly
decreased
the
wild-
type
CCND
1
promoter
activity
and
down-regulated
the
expression
of
CCND
1
,
but
did
not
affect
the
activity
of
the
mutant
promoter
.
Whereas
,
suppression
of
CCND
1
did
not
affect
OCT
4
expression
,
suggesting
that
OCT
4
regulates
CCND
1
expression
by
activating
the
CCND
1
promoter
and
subsequently
promoting
cell
cycle
progression
.
The
results
revealed
and
confirmed
that
OCT
4
is
the
upstream
factor
that
directly
binds
to
the
CCND
1
promoter
to
regulate
CCND
1
expression
,
then
to
promote
cell
cycle
progression
and
accelerate
the
proliferation
and
invasion
of
esophageal
cancer
cells
.
This
finding
may
significantly
contribute
to
elucidating
the
regulatory
mechanism
involved
in
the
cell
cycle
progression
of
esophageal
cancer
cells
and
may
aid
in
screening
potential
gene
targets
for
the
biological
therapy
of
esophageal
cancer
.
Diseases
Validation
Diseases presenting
"directly binds"
symptom
esophageal carcinoma
wiskott-aldrich syndrome
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