Frontiers in Oncology,
Journal Year:
2024,
Volume and Issue:
14
Published: June 14, 2024
Background
Hepatoblastoma
(HB)
is
the
most
common
pediatric
hepatic
malignancy.
Despite
progress
in
HB
treatment,
investigating
pathomechanisms
to
optimize
stratification
and
therapies
remains
a
focal
point
improve
outcome
for
high-risk
patients.
Methods
Here,
we
pointed
explore
impact
of
these
mechanisms
HB.
An
observational
study
was
performed
on
liver
samples
from
cohort
17
patients
with
diagnosis
two
normal
samples.
The
vitro
experiments
were
executed
Huh6
human
cell
line
treated
FAK
inhibitor
TAE226.
Results
Our
results
highlight
significant
up-regulation
mRNA
protein
expression
livers
respect
livers.
increased
total
Tyr397
phosphorylated
(pTyr397FAK)
significantly
correlated
some
epigenetic
regulators
histone
H3
methylation
acetylation.
Of
note,
pTyr397FAK,
N-methyltransferase
enzyme
(EZH2)
tri-methylation
H3K27
residue
tumor
size
alpha-fetoprotein
(AFP)
levels.
Finally,
TAE226
caused
reduction
regulators,
AFP
,
EPCAM
OCT4
SOX2
association
anti-proliferative
pro-apoptotic
effects
cells.
Conclusion
suggest
role
that
requires
further
investigations
mainly
focused
exploration
its
effective
diagnostic
therapeutic
translatability.
Molecular Carcinogenesis,
Journal Year:
2023,
Volume and Issue:
62(10), P. 1460 - 1473
Published: June 6, 2023
Abstract
RAB6A
is
a
member
of
RAB
GTPase
family
and
plays
an
important
role
in
the
targeted
transport
neurotrophic
receptors
inflammatory
cytokines.
RAB6A‐mediated
secretory
pathway
involved
many
physiological
pathological
processes.
Defects
may
lead
to
development
diseases,
including
cancer.
However,
its
cholangiocarcinoma
(CCA)
has
not
yet
been
revealed.
We
explored
regulatory
stem‐like
subsets
CCA.
showed
that
knockdown
(KD)
impedes
cancer
stem
cells
(CSCs)
properties
epithelial−mesenchymal
transition
vitro
suppression
inhibits
tumor
growth
vivo.
screened
target
cargos
CCA
identified
extracellular
matrix
component
as
cargo.
binds
directly
OPN,
KD
suppressed
OPN
secretion
inhibited
interaction
between
αV
integrin
receptor.
Moreover,
AKT
signaling
pathway,
which
downstream
effector
receptor
signaling.
In
addition,
shRNA
targeting
blocked
endogenous
expression
consequently
weakened
CSCs
RAB6A‐formed
spheres.
Similarly,
inhibitor
signaling,
MK2206
also
oncogenic
function
cells.
conclusion,
our
findings
sustains
phenotype
maintenance
by
modulating
consequentially
activating
pathway.
Targeting
RAB6A/OPN
axis
be
effective
strategy
for
therapy.
Translational Cancer Research,
Journal Year:
2023,
Volume and Issue:
12(5), P. 1210 - 1231
Published: April 14, 2023
Background:
Hepatocellular
carcinoma
(HCC)
is
a
malignant
disease
with
poor
prognosis.Among
the
treatment
strategies
for
HCC,
tumor
immunotherapy
(TIT)
promising
research
hotspot,
in
which
identifying
novel
immune-related
biomarkers
and
selecting
suitable
patient
population
are
urgent
issues
to
be
solved.Methods:
In
this
study,
an
abnormal
expression
map
of
HCC
cell
genes
was
constructed
using
public
high-throughput
data
from
7,384
samples
(3,941
vs.
3,.Through
singlecell
RNA
sequencing
(scRNA-seq)
trajectory
analysis,
defined
as
potential
drivers
differentiation
development
were
selected.By
screening
both
those
associated
high
development,
series
target
identified.Coexpression
analysis
performed
Multiscale
Embedded
Gene
Co-expression
Network
Analysis
(MEGENA)
find
specific
candidate
involved
similar
biological
processes.Subsequently,
nonnegative
matrix
factorization
(NMF)
conducted
select
patients
based
on
coexpression
network
genes.Results:
HSP90AA1,
CDK4,
HSPA8,
HSPH1,
HSPA5
identified
prognosis
prediction
HCC.Through
use
our
molecular
classification
system,
function
module
containing
5
genes,
characteristics
found
candidates
TIT.Conclusions:
These
findings
provide
new
insights
into
selection
populations
future
immunotherapy.
BioMed Research International,
Journal Year:
2022,
Volume and Issue:
2022, P. 1 - 28
Published: Oct. 5, 2022
Hepatocellular
carcinoma
(HCC)
is
one
of
the
most
lethal
cancers
worldwide,
which
associated
with
a
variety
risk
factors.
Cancer
stem
cells
are
self-renewal
cells,
can
promote
occurrence
and
metastasis
tumors
enhance
drug
resistance
tumor
treatment.
This
study
aimed
to
develop
stemness
score
model
assess
prognosis
hepatocellular
patients
for
optimization
The
single-cell
sequencing
data
GSE149614
was
downloaded
from
GEO
database.
Then,
we
compared
gene
expression
hepatic
other
hepatocytes
in
samples
screen
differentially
expressed
genes
related
stemness.
R
package
“clusterProfiler”
used
explore
potential
function
stemness-related
genes.
We
then
constructed
prognostic
using
LASSO
regression
analysis
based
on
TCGA
GSE14520
cohorts.
associations
clinical
features,
sensitivity,
mutation,
immune
microenvironment
were
further
explored.
“rms”
construct
nomogram
model.
A
total
18
enrolled
Kaplan-Meier
proved
good
performance
at
predicting
overall
survival
(OS)
HCC
patients.
closely
HCC.
infiltration
level
CD8+
T
lower,
tumor-associated
macrophages
higher
high-stemness
score,
indicating
an
immunosuppressive
microenvironment.
Our
established
that
reliably
predicts
OS
findings
may
help
clarify
biological
characteristics
progression
future
diagnosis
therapy
Genes & Diseases,
Journal Year:
2024,
Volume and Issue:
12(3), P. 101311 - 101311
Published: April 17, 2024
The
ubiquitin
(Ub)
system,
a
ubiquitous
presence
across
eukaryotes,
plays
crucial
role
in
the
precise
orchestration
of
diverse
cellular
protein
processes.
From
steering
signaling
pathways
and
orchestrating
cell
cycle
progression
to
guiding
receptor
trafficking
modulating
immune
responses,
this
process
regulating
various
biological
functions.
dysregulation
Ub-mediated
prevalent
cancers
ushers
spectrum
clinical
outcomes
ranging
from
tumorigenesis
metastasis
recurrence
drug
resistance.
Ubiquitination,
linchpin
mediated
by
Ub,
assumes
central
mantle
molding
dynamics.
It
navigates
transitions
cues
ultimately
shapes
destiny
proteins.
Recent
years
have
witnessed
an
upsurge
momentum
surrounding
development
protein-based
therapeutics
aimed
at
targeting
Ub
system
under
sway
cancer
stem
cells.
article
provides
comprehensive
overview
ongoing
in-depth
discussions
regarding
regulation
its
impact
on
Amidst
tapestry
insights,
delves
into
expansive
roles
E3
ligases,
deubiquitinases,
transcription
factors
entwined
with
Furthermore,
spotlight
turns
interplay
pivotal
Notch,
Hedgehog,
Wnt/β-catenin,
Hippo-YAP
all
play
cells
followed
specific
modulation
Ub-proteasome.
Frontiers in Oncology,
Journal Year:
2024,
Volume and Issue:
14
Published: June 14, 2024
Background
Hepatoblastoma
(HB)
is
the
most
common
pediatric
hepatic
malignancy.
Despite
progress
in
HB
treatment,
investigating
pathomechanisms
to
optimize
stratification
and
therapies
remains
a
focal
point
improve
outcome
for
high-risk
patients.
Methods
Here,
we
pointed
explore
impact
of
these
mechanisms
HB.
An
observational
study
was
performed
on
liver
samples
from
cohort
17
patients
with
diagnosis
two
normal
samples.
The
vitro
experiments
were
executed
Huh6
human
cell
line
treated
FAK
inhibitor
TAE226.
Results
Our
results
highlight
significant
up-regulation
mRNA
protein
expression
livers
respect
livers.
increased
total
Tyr397
phosphorylated
(pTyr397FAK)
significantly
correlated
some
epigenetic
regulators
histone
H3
methylation
acetylation.
Of
note,
pTyr397FAK,
N-methyltransferase
enzyme
(EZH2)
tri-methylation
H3K27
residue
tumor
size
alpha-fetoprotein
(AFP)
levels.
Finally,
TAE226
caused
reduction
regulators,
AFP
,
EPCAM
OCT4
SOX2
association
anti-proliferative
pro-apoptotic
effects
cells.
Conclusion
suggest
role
that
requires
further
investigations
mainly
focused
exploration
its
effective
diagnostic
therapeutic
translatability.