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Reduction of TIP30 in esophageal squamous cell carcinoma cells involves promoter methylation and microRNA-10b.
[esophageal squamous cell carcinoma]
TIP
30
is
a
putative
tumor
suppressor
that
can
promote
apoptosis
and
inhibit
angiogenesis
.
However
,
the
role
of
TIP
30
in
esophageal
squamous
cell
carcinoma
(
ESCC
)
biology
has
not
been
investigated
.
Immunohistochemistry
was
used
to
investigate
the
expression
of
TIP
30
in
70
ESCC
.
Hypermethylation
of
TIP
30
was
evaluated
by
the
methylation
specific
PCR
(
MSP
)
method
in
ESCC
(
tumor
and
paired
adjacent
non-
tumor
tissues
)
.
Lost
expression
of
TIP
30
was
observed
in
50
of
70
(
71
.
4
%
)
ESCC
.
61
.
4
%
(
43
of
70
)
of
primary
tumors
analyzed
displayed
TIP
30
hypermethylation
,
indicating
that
this
aberrant
characteristic
is
common
in
ESCC
.
Moreover
,
a
statistically
significant
inverse
association
was
found
between
TIP
30
methylation
status
and
expression
of
the
TIP
30
protein
in
tumor
tissues
(
p
=
0
.
001
)
.
We
also
found
that
microRNA-
10
b
(
miR-
10
b
)
targets
a
homologous
DNA
region
in
the
3
'
untranslated
region
of
the
TIP
30
gene
and
represses
its
expression
at
the
transcriptional
level
.
Reporter
assay
with
3
'
UTR
of
TIP
30
cloned
downstream
of
the
luciferase
gene
showed
reduced
luciferase
activity
in
the
presence
of
miR-
10
b
,
providing
strong
evidence
that
miR-
10
b
is
a
direct
regulator
of
TIP
30
.
These
results
suggest
that
TIP
30
expression
is
regulated
by
promoter
methylation
and
miR-
10
b
in
ESCC
.
