Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Фев. 19, 2024
Abstract
Extramammary
Paget
disease
(EMPD)
is
a
rare
skin
cancer
that
primarily
affects
older
individuals
predominantly
in
areas
with
apocrine
sweat
glands.
Although
most
early
EMPD
lesions
are
indolent,
patients
metastatic
have
poor
prognosis
due
to
the
lack
of
effective
systemic
treatment.
In
this
study,
we
investigated
role
forkhead
box
M1
(FOXM1),
potent
transcription
factor,
and
assessed
potential
FOXM1
as
therapeutic
target.
Immunohistochemistry
112
primary
17
samples
revealed
expression
increased
tumor
progression.
Patients
whom
was
expressed
more
than
10%
cells
had
significantly
shorter
disease-specific
survival
other
(
p
=
0.0397).
vitro
studies
using
our
newly
established
cell
line,
KS-EMPD-1,
found
high
FOXM1.
Knockdown
impaired
viability,
migration,
invasion.
Inhibition
thiostrepton
also
reduced
viability
dose-dependent
manner.
These
findings
suggest
promising
target
for
EMPD.
In
the
present
study,
we
explored
potential
of
coumarin-based
compounds,
known
for
their
potent
anticancer
properties,
by
designing
and
synthesizing
a
novel
category
8-methoxycoumarin-3-carboxamides.
Our
aim
was
to
investigate
antiproliferative
activity
against
liver
cancer
cells.
Toward
this,
developed
versatile
synthetic
approach
produce
series
8-methoxycoumarin-3-carboxamide
analogues
with
meticulous
structural
features.
Assessment
demonstrated
significant
inhibitory
effects
on
growth
HepG2
cells,
widely
studied
cell
line.
Among
screened
compound
5
exhibited
most
among
compounds
(IC50
=
0.9
µM),
outperforming
drug
staurosporine
8.4
while
showing
minimal
impact
normal
The
flow
cytometric
analysis
revealed
that
induces
cycle
arrest
during
G1/S
phase
triggers
apoptosis
in
cells
increasing
percentage
arrested
G2/M
pre-G1
phases.
Annexin
V-FITC/PI
screening
further
supported
induction
without
necrosis.
Further,
ability
activate
caspase3/7
protein
substantially
inhibited
β-tubulin
polymerization
Finally,
molecular
modelling
affirmed
high
binding
affinity
toward
active
cavity
protein,
suggesting
its
mechanistic
involvement.
Collectively,
our
findings
highlight
therapeutic
presented
class
coumarin
analogues,
especially
5,
as
promising
candidates
development
effective
anti-hepatocellular
carcinoma
agents.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(20), С. 15173 - 15173
Опубликована: Окт. 14, 2023
Despite
their
clonal
origins,
tumors
eventually
develop
into
complex
communities
made
up
of
phenotypically
different
cell
subpopulations,
according
to
mounting
evidence.
Tumor
cell-intrinsic
programming
and
signals
from
geographically
temporally
changing
microenvironments
both
contribute
this
variability.
Furthermore,
the
mutational
load
is
typically
lacking
in
childhood
malignancies
adult
cancers,
they
still
exhibit
high
cellular
heterogeneity
levels
largely
mediated
by
epigenetic
mechanisms.
Ewing
sarcomas
represent
highly
aggressive
affecting
bone
soft
tissue,
primarily
afflicting
adolescents.
Unfortunately,
outlook
for
patients
facing
relapsed
or
metastatic
disease
grim.
These
are
fueled
a
distinctive
fusion
event
involving
an
FET
protein
ETS
family
transcription
factor,
with
most
prevalent
being
EWS/FLI1.
originating
common
driver
mutation,
sarcoma
cells
display
significant
variations
transcriptional
activity,
within
among
tumors.
Recent
research
has
pinpointed
distinct
activities
as
principal
source
heterogeneity,
resulting
markedly
diverse
phenotypes.
In
review,
we
aim
characterize
role
EWS/FLI
exploring
its
general
mechanism
activation
elucidating
implications
tumor
heterogeneity.
Additionally,
delve
potential
therapeutic
opportunities
target
aberrant
context
treatment.
Frontiers in Bioinformatics,
Год журнала:
2025,
Номер
5
Опубликована: Янв. 28, 2025
Background
Small
cell
carcinoma
of
the
esophagus
(SCCE)
is
a
rare
form
esophageal
cancer,
which
also
belongs
to
category
neuroendocrine
malignant
tumors,
with
low
incidence
but
high
aggressiveness,
and
very
poor
prognosis
for
patients.
Currently,
there
lack
unique
staging
treatment
guidelines
SCCE.
Therefore,
deeper
understanding
therapeutic
targets
mechanisms
underlying
its
occurrence
development
great
importance
early
diagnosis,
identification
potential
agents
improvement
Methods
Firstly,
dataset
SCCE
was
downloaded
from
GEO
database
GEO2R
tool
employed
analysis
differentially
expressed
genes
(DEGs).
GO
KEGG
DEGs
were
carried
out
by
using
Bioinformatics
OmicStudio
tools.
Then,
up-
down-regulated
intersected
oncogenes
tumor
suppressor
respectively,
obtain
onco/tumor
in
The
STRING
conduct
protein-protein
interaction
(PPI)
genes,
network
further
constructed
Cytoscape,
hub
obtained
through
Cytohubba
plugin.
In
addition,
miRDB,
miRwalk,
Targetscan,
OncomiR,
starbase,
Lncbase
used
predict
miRNAs
lncRNAs
that
regulate
ceRNA
built
based
on
this.
Transcription
factor-miRNA
co-regulatory
analyzed
NetworkAnalyst
embellished
Cytoscape.
Finally,
drugs
may
target
searched
DGIdb
ConnectivityMAP,
docking
verification
performed
Schrodinger.
Results
A
total
820
upregulated
716
downregulated,
these,
54
identified
as
85
genes.
Seven
PPI
network,
AURKA,
BIRC5
,
CDK1
EZH2
FOXM1
KLF4
UBE2C
.
Furthermore,
38
filtered
molecular
results
score
AURKA
multiple
(<6).
crizotinib
lapatinib
CDK1,
rucaparib
EZH2,
lowest
energy
all
results.
Conclusion
are
SCCE,
among
them,
be
drugs.
Crizotinib,
lapatinib,
can
act
above
inhibit
progression
play
role.
International Journal of Biological Sciences,
Год журнала:
2025,
Номер
21(3), С. 1047 - 1064
Опубликована: Янв. 13, 2025
Pancreatic
ductal
adenocarcinoma
(PDAC)
remains
a
highly
lethal
malignancy
with
limited
treatment
options.
Investigating
novel
therapeutic
targets
and
understanding
mechanisms
of
chemoresistance
are
crucial
for
improving
patient
outcomes.
This
study
investigated
the
role
CKS1B
in
PDAC
carcinogenesis,
stemness
chemoresistance,
explores
underlying
driving
its
upregulation.
The
findings
may
provide
insights
potential
strategies
PDAC.
Methods:
expression
was
analyzed
tissues
cell
lines,
impact
on
proliferation,
migration,
apoptosis,
chemosensitivity
were
evaluated
by
using
vitro
vivo
models,
mechanistic
connection
to
transcription
factor
FOXM1
explored
molecular
biology
methods.
Results:
significantly
upregulated
correlated
poor
survival.
promoted
inhibited
apoptosis.
Expression
enhanced
properties
pancreatic
cancer.
knockdown
sensitized
cells
gemcitabine
oxaliplatin.
Mechanistically,
is
transcriptionally
regulated
FOXM1,
establishing
FOXM1-CKS1B
signaling
axis
that
regulates
stemness,
drug
resistance
Conclusions:
Our
strongly
suggest
plays
critical
progression,
chemoresistance.
Targeting
represents
promising
strategy
patients.
