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A random Abstract
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RNAi screening identifies HAT1 as a potential drug target in esophageal squamous cell carcinoma.
[esophageal carcinoma]
Esophageal
carcinoma
(
EC
)
is
one
of
the
most
fatal
carcinomas
of
the
gastrointestinal
tract
.
Aberrant
activity
of
histone
acetyltransferases
(
HATs
)
/
deacetylases
(
HDACs
)
play
a
critical
role
in
carcinogenesis
through
the
regulation
of
the
genes
involved
in
cell
differentiation
,
proliferation
,
and
apoptosis
.
However
,
cellular
functions
of
HATs
/
HDACs
in
esophageal
cancer
and
its
molecular
mechanisms
remain
unclear
.
An
RNAi
screen
was
used
in
this
study
to
identify
the
histone
acetyltransferases
(
HATs
)
and
deacetylases
(
HDACs
)
that
could
be
critical
for
the
survival
of
EC
cells
.
We
demonstrated
that
HAT
1
(
histone
acetyltransferase
1
)
was
an
important
determinant
to
regulate
the
proliferation
of
human
EC
Eca-
109
cells
.
Furthermore
,
we
showed
that
the
knockdown
of
HAT
1
induced
a
G
2
/
M
cell
cycle
arrest
,
which
was
associated
with
the
disruption
of
cell
cycle-related
events
,
including
the
decrease
of
cyclinD
1
as
well
as
alteration
in
cyclinB
1
expression
.
The
expression
of
HAT
1
was
validated
to
be
higher
in
the
primary
tumors
and
adjacent
tissue
as
compared
to
that
of
the
normal
esophageal
tissue
.
Furthermore
,
we
found
that
HAT
1
expression
was
directly
correlated
with
the
poor
tumor
differentiation
of
EC
tissue
,
which
suggested
that
HAT
1
played
an
important
role
in
esophageal
carcinoma
and
that
it
could
be
a
novel
EC
therapeutic
target
.
