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WHSC1 Promotes Oncogenesis through Regulation of NIMA-related-kinase-7 in Squamous Cell Carcinoma of the Head and Neck.
[wolf-hirschhorn syndrome]
Squamous
cell
carcinoma
of
the
head
and
neck
(
SCCHN
)
is
a
relatively
common
malignancy
with
suboptimal
long
-term
prognosis
,
thus
new
treatment
strategies
are
urgently
needed
.
Over
the
last
decade
,
histone
methyltransferases
(
HMTs
)
have
been
recognized
as
promising
targets
for
cancer
therapy
,
but
their
mechanism
of
action
in
most
solid
tumors
,
including
SCCHN
,
remains
to
be
elucidated
.
This
study
investigated
the
role
of
Wolf-
Hirschhorn
syndrome
candidate
1
(
WHSC
1
)
,
a
NSD-family
histone
methyltransferase
,
in
SCCHN
.
Immunohistochemical
(
IHC
)
analysis
of
locoregionally
advanced
SCCHN
,
dysplastic
and
normal
epithelial
tissue
specimens
revealed
that
WHSC
1
expression
and
dimethylation
of
histone
H
3
lysine
36
(
H
3
K
36
me
2
)
were
significantly
higher
in
SCCHN
tissues
compared
with
normal
epithelium
.
Both
WHSC
1
expression
and
H
3
K
36
me
2
levels
were
significantly
correlated
with
histological
grade
.
WHSC
1
knockdown
in
multiple
SCCHN
cell
lines
resulted
in
significant
growth
suppression
,
induction
of
apoptosis
and
delay
of
the
cell
cycle
progression
.
Immunoblot
and
immunocytochemical
analyses
in
SCCHN
cells
demonstrated
that
WHSC
1
induced
H
3
K
36
me
2
and
H
3
K
36
me
3
.
Microarray
expression
profile
analysis
revealed
NIMA
-related-kinase-
7
(
NEK
7
)
to
be
a
downstream
target
gene
of
WHSC
1
,
and
chromatin
immunoprecipitation
(
ChIP
)
assays
showed
that
NEK
7
was
directly
regulated
by
WHSC
1
through
H
3
K
36
me
2
.
Furthermore
,
similar
to
WHSC
1
,
NEK
7
knockdown
significantly
reduced
cell
cycle
progression
,
indicating
that
NEK
7
is
a
key
player
in
the
molecular
pathway
regulated
by
WHSC
1
.
Implications
:
WHSC
1
possesses
oncogenic
functions
in
SCCHN
and
represents
a
potential
molecular
target
for
the
treatment
of
SCCHN
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated