bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 16, 2024
SUMMARY
Gastric
cancer
(GC)
is
the
fifth
most
common
human
worldwide,
but
genetic
etiology
largely
unknown.
We
performed
a
Bayesian
genome-wide
association
study
and
selection
analyses
in
naturally-occurring
canine
model
of
GC,
Belgian
Tervuren
Sheepdog
breeds,
to
elucidate
underlying
risk
factors.
identified
15
loci
with
over
90%
predictive
accuracy
for
GC
phenotype.
Variant
filtering
revealed
germline
putative
regulatory
variants
EPAS1
(
HIF2A
)
PTEN
genes
coding
variant
CD101
.
Although
closely
related
Sheepdogs,
Malinois
rarely
develop
GC.
Across-breed
uncovered
protective
haplotypes
under
at
SOX2-OT
IGF2BP2
Among
HDAC2
were
present
comparatively
high
frequency
associated
Here,
we
describe
complex
architecture
governing
dog
model,
including
such
as
PDZRN3
,
that
have
not
been
Cell Death Discovery,
Год журнала:
2025,
Номер
11(1)
Опубликована: Янв. 18, 2025
Helicobacter
pylori
(H.
pylori)
plays
an
important
role
in
the
malignant
transformation
of
gastric
mucosa
from
chronic
inflammation
to
cancer.
However,
mechanisms
underlying
epigenetic
regulation
carcinogenesis
mediated
by
H.
remain
unclear.
Here,
we
uncover
that
inhibits
METTL14
upregulating
ATF3.
cancer
(GC)
cell
proliferation
and
metastasis
vitro
vivo.
Downregulation
Vesicle-associated
membrane
protein-3
(VAMP3)
reducing
m6A
modification
level
VAMP3
mRNA
stability
IGF2BP2-dependent
mRNA.
also
accelerates
progression
GC
regulating
VAMP3/LC3C-mediated
c-Met
recycling.
Moreover,
expression
Hp+
gastritis
tissues
is
much
lower
than
Hp-
tissues.
levels
are
downregulated
notably
cancerous
patients
with
GC.
Therefore,
our
results
show
a
novel
METTL14-VAMP3-LC3C-c-Met
signalling
axis
development
infection,
which
reveals
mechanism
for
provides
potential
prognostic
biomarkers
progression.
European journal of medical research,
Год журнала:
2025,
Номер
30(1)
Опубликована: Фев. 12, 2025
The
significance
of
m6A
modifications
in
several
biological
processes
has
been
increasingly
recognized,
particularly
the
context
cancer.
For
instance,
gastric
cancer
(GC)
have
significantly
implicated
tumor
progression,
metastasis,
and
treatment
resistance.
GC
is
characterized
by
differential
expression
regulators.
High
writers
such
as
METTL3
WTAP
are
associated
with
poor
prognosis
aggressive
clinical
features.
Conversely,
low
METTL14
linked
to
worse
outcomes,
whereas
elevated
levels
demethylases,
FTO
ALKBH5,
correlate
better
survival
rates.
These
regulators
influence
cellular
functions,
including
proliferation,
invasion,
migration,
glycolysis,
chemotherapy
resistance,
thereby
affecting
growth
therapeutic
outcomes.
assessment
modification
patterns
profiles
m6A-related
genes
hold
substantial
potential
for
improving
diagnosis
GC.
In
this
review,
we
provide
an
updated
comprehensive
summary
role
GC,
emphasizing
their
molecular
mechanisms,
significance,
translational
applications
developing
novel
diagnostic
strategies.
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 2, 2025
Abstract
Gastric
cancer
(GC)
is
a
leading
cause
of
cancer-related
deaths
worldwide,
especially
in
East
Asia,
with
low
5-year
survival
rate
due
to
late-stage
diagnosis.
Identifying
molecular
mechanisms
that
regulate
GC
progression
critical
for
improving
clinical
outcomes.
RNF81,
member
the
tripartite
motif
(TRIM)
family,
has
demonstrated
diverse
roles
various
cancers.
In
this
study,
we
uncover
its
tumor-suppressive
function
through
novel
regulatory
pathways.
Analysis
data
and
tissue
microarrays
revealed
RNF81
expression
significantly
downregulated
tissues
positively
correlates
patient
survival.
Mechanistically,
identified
lysine
demethylase
KDM1A
as
key
repressor
expression.
recruits
transcription
factor
E2F1
form
transcriptional
complex,
reducing
H3K4me1
H3K4me2
levels
at
promoter.
Functional
studies
showed
stabilizes
tumor
suppressor
KLF4
by
binding
SPRY
domain,
thereby
inhibiting
ubiquitination
degradation.
Overexpression
suppressed
cell
proliferation,
migration,
invasion
vitro
reduced
growth
vivo,
effects
were
partially
rescued
knockdown.
These
findings
reveal
KDM1A-RNF81-KLF4
axis
highlight
potential
therapeutic
target
treatment.
Targeting
pathway
may
offer
promising
strategies
improve
outcomes
patients.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 6, 2025
Krüppel-like
factors
(KLFs)
regulate
various
biological
processes
such
as
cell
proliferation,
migration,
invasion,
and
differentiation
gene
transcription
factors.
Signaling
pathways
which
mediated
by
KLF4
have
a
sophisticated
role
in
tumors
due
to
multiple
factors,
including
the
types
or
stage
of
tumors.
plays
promoter
tumorigenesis
development,
tumor
suppressor
context-dependent
anti-
pro-inflammatory
factor.
over-expression
increases
CD8+T
enhances
antitumor
immunity.
This
review
aims
provide
information
about
relationship
immunity
with
guide
future
study.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 17, 2025
Hepatocellular
carcinoma
(HCC)
is
the
most
prevalent
primary
liver
malignancy
and
a
leading
cause
of
cancer-related
deaths
globally.
The
asymptomatic
progression
early-stage
HCC
often
results
in
diagnosis
at
advanced
stages,
significantly
limiting
therapeutic
options
worsening
prognosis.
Immunotherapy,
with
immune
checkpoint
inhibitors
(ICIs)
forefront,
has
revolutionized
treatment.
Nevertheless,
tumor
heterogeneity,
evasion,
presence
immunosuppressive
components
within
microenvironment
(TIME)
continue
to
compromise
its
efficacy.
Furthermore,
resistance
or
non-responsiveness
ICIs
some
patients
underscores
urgent
need
unravel
complexities
TIME
design
innovative
strategies
that
enhance
immunotherapeutic
outcomes.
Emerging
evidence
revealed
pivotal
role
N6-methyladenosine
(m6A),
prominent
RNA
methylation
modification,
shaping
HCC.
By
regulating
stability
translation,
m6A
influences
immune-related
factors,
including
cytokines
molecules.
This
modification
governs
PD-L1
expression,
facilitating
escape
contributing
against
ICIs.
Advances
this
field
have
also
identified
m6A-related
regulators
as
promising
biomarkers
for
predicting
immunotherapy
response
potential
targets
optimizing
treatment
review
examines
regulatory
mechanisms
HCC,
focus
on
impact
cells
cytokine
dynamics.
It
explores
targeting
pathways
improve
efficacy
outlines
emerging
directions
future
research.
These
insights
aim
provide
foundation
developing
novel
overcome
advance
Journal of Biochemical and Molecular Toxicology,
Год журнала:
2024,
Номер
38(10)
Опубликована: Сен. 12, 2024
Macrophage
polarization
and
inflammation
may
play
an
important
role
in
the
development
of
sepsis.
T-cell
immunoglobulin
mucin
1
(TIM1)
has
been
demonstrated
to
promote
macrophage
inflammatory
responses.
However,
whether
TIM1
regulates
affect
sepsis
remains
unclear.
Human
monocytic
leukemia
cell
line
was
induced
into
macrophages,
followed
by
stimulated
with
LPS
IL-4
induce
M1
M2
polarization.
The
expression
levels
TIM1,
methyltransferase
3
(METTL3),
insulin
like
growth
factor
2
mRNA
binding
protein
(IGF2BP2)
were
examined
qRT-PCR
western
blot.
IL-6,
IL-1β,
TNF-α
tested
ELISA.
CD86
