World Journal of Gastroenterology,
Год журнала:
2025,
Номер
31(11)
Опубликована: Март 12, 2025
BACKGROUND
The
causes
of
death
in
patients
with
advanced
esophageal
cancer
are
multifactorial,
tumor
metastasis
being
one
the
important
factors.
Histone
acetylation
promotes
migration
squamous
cell
carcinoma
(ESCC)
cells,
while
histone
deacetylase
inhibitor
(HDACi)
shows
complex
effects
on
functions.
AIM
To
comprehensively
elucidate
impact
and
molecular
mechanisms
trichostatin
A
(TSA),
an
HDACi,
ESCC
through
bromodomain-containing
protein
(BRD4)/cellular
myelocytomatosis
oncogene
(c-Myc)/endoplasmic
reticulum
(ER)-stress.
METHODS
TSA
lines
Eca109
EC9706
were
evaluated
using
Transwell
assays,
small
interfering
transfection
pathway-specific
inhibitors
to
underlying
mechanisms.
mRNA
levels
involved
examined
by
quantitative
real-time
polymerase
chain
reaction.
Protein
acetylated
histones
H3
(acH3)
H4,
BRD4,
c-Myc,
as
well
markers
ER
stress
epithelial-mesenchymal
transition
(EMT),
analyzed
western
blot.
Additionally,
this
method
was
also
used
examine
acH3
tissues
adjacent
tissues.
Patient
outcomes
subsequently
tracked
identify
prognostic
indicators
Log-Rank
tests
Cox
multivariate
analysis.
RESULTS
promoted
cells
stimulating
EMT
process.
TSA-mediated
facilitated
recruitment
a
protein,
triggering
expression
c-Myc.
This
cascade
induced
enhanced
cells.
further
mechanism,
we
employed
various
interventions
including
4-phenylbutyric
acid,
knockdown
c-Myc
BRD4
expression,
utilization
carboxylic
acid
1.
Mechanistically,
these
studies
revealed
that
which
turn
triggered
sequential
activation
EMT,
thereby
promoting
specimens
from
43
ESCC,
both
paired
Statistical
analysis
unveiled
negative
correlation
between
level
long-term
prognosis
ESCC.
CONCLUSION
BRD4/c-Myc/ER
pathway.
Moreover,
elevated
correlated
poor
prognosis.
These
findings
enhance
our
understanding
HDACi
therapy.
Molecular Biomedicine,
Год журнала:
2023,
Номер
4(1)
Опубликована: Авг. 24, 2023
Abstract
RNA
modifications
are
dynamic
and
reversible
chemical
on
substrate
that
regulated
by
specific
modifying
enzymes.
They
play
important
roles
in
the
regulation
of
many
biological
processes
various
diseases,
such
as
development
cancer
other
diseases.
With
help
advanced
sequencing
technologies,
role
has
caught
increasing
attention
human
diseases
scientific
research.
In
this
review,
we
briefly
summarized
basic
mechanisms
several
common
modifications,
including
m6A,
m5C,
m1A,
m7G,
Ψ,
A-to-I
editing
ac4C.
Importantly,
discussed
their
potential
functions
cancer,
neurological
disorders,
cardiovascular
metabolic
genetic
developmental
well
immune
disorders.
Through
“writing-erasing-reading”
mechanisms,
regulate
stability,
translation,
localization
pivotal
disease-related
mRNAs
to
manipulate
disease
development.
Moreover,
also
highlighted
review
all
currently
available
RNA-modifier-targeting
small
molecular
inhibitors
or
activators,
most
which
designed
against
m6A-related
enzymes,
METTL3,
FTO
ALKBH5.
This
provides
clues
for
clinical
therapy
future
study
directions
modification
field.
More
in-depth
studies
further
activators
needed
a
thorough
understanding
epitranscriptomics
diagnosis,
treatment,
prognosis
Liver International,
Год журнала:
2024,
Номер
44(8), С. 1808 - 1831
Опубликована: Май 3, 2024
Hepatocellular
carcinoma
(HCC),
one
of
the
most
prevalent
and
destructive
causes
cancer-related
deaths
worldwide,
approximately
70%
patients
with
HCC
exhibit
advanced
disease
at
diagnosis,
limiting
potential
for
radical
treatment.
For
such
patients,
lenvatinib,
a
long-awaited
alternative
to
sorafenib
first-line
targeted
therapy,
has
become
key
Unfortunately,
despite
some
progress,
prognosis
remains
poor
because
drug
resistance
development.
However,
molecular
mechanisms
underlying
lenvatinib
ways
relief
in
are
largely
unknown
lack
systematic
summary;
thus,
this
review
not
only
aims
explore
factors
contributing
HCC,
but
more
importantly,
summary
methods
conquer
or
mitigate
resistance.
The
results
suggest
that
abnormal
activation
pathways,
transport,
epigenetics,
tumour
microenvironment,
cancer
stem
cells,
regulated
cell
death,
epithelial-mesenchymal
transition,
other
involved
development
subsequent
progression.
To
improve
therapeutic
outcomes
inhibiting
acquired
resistance,
combined
therapies,
nano-delivery
carriers
may
be
possible
approaches.
Cancer Communications,
Год журнала:
2024,
Номер
44(9), С. 1018 - 1041
Опубликована: Июль 19, 2024
Abstract
Background
N4‐acetylcytidine
(ac4C)
represents
a
novel
messenger
RNA
(mRNA)
modification,
and
its
associated
acetyltransferase
N‐acetyltransferase
10
(NAT10)
plays
crucial
role
in
the
initiation
progression
of
tumors
by
regulating
mRNA
functionality.
However,
hepatocellular
carcinoma
(HCC)
development
prognosis
is
largely
unknown.
This
study
aimed
to
elucidate
NAT10‐mediated
ac4C
HCC
provide
promising
therapeutic
approach.
Methods
The
levels
were
evaluated
dot
blot
ultra‐performance
liquid
chromatography‐tandem
mass
spectrometry
with
harvested
tissues.
expression
NAT10
was
investigated
using
quantitative
real‐time
polymerase
chain
reaction,
western
blotting,
immunohistochemical
staining
across
91
cohorts
patients.
To
explore
underlying
mechanisms
NAT10‐ac4C
HCC,
we
employed
comprehensive
approach
integrating
acetylated
immunoprecipitation
sequencing,
sequencing
ribosome
profiling
analyses,
along
immunoprecipitation,
pull‐down,
spectrometry,
site‐specific
mutation
analyses.
drug
affinity
responsive
targets
stability,
cellular
thermal
shift
assay,
surface
plasmon
resonance
assays
performed
assess
specific
binding
Panobinostat.
Furthermore,
efficacy
targeting
for
treatment
elucidated
through
vitro
experiments
cells
vivo
mouse
models.
Results
Our
investigation
revealed
significant
increase
both
level
HCC.
Notably,
elevated
poor
outcomes
Functionally,
silencing
suppressed
proliferation
metastasis
vivo.
Mechanistically,
stimulates
modification
within
coding
sequence
(CDS)
high
mobility
group
protein
B2
(HMGB2),
which
subsequently
enhances
HMGB2
translation
facilitating
eukaryotic
elongation
factor
2
(eEF2)
sites
on
mRNA's
CDS.
Additionally,
high‐throughput
compound
library
screening
Panobinostat
as
potent
inhibitor
modification.
inhibition
significantly
attenuated
growth
Conclusions
identified
oncogenic
epi‐transcriptome
axis
involving
NAT10‐ac4C/eEF2‐HMGB2,
pivotal
metastasis.
validates
potential
this
treatment.
BMC Cardiovascular Disorders,
Год журнала:
2024,
Номер
24(1)
Опубликована: Март 27, 2024
Background
Myocardial
ischemia
is
a
prevalent
cardiovascular
disorder
associated
with
significant
morbidity
and
mortality.
While
prompt
restoration
of
blood
flow
essential
for
improving
patient
outcomes,
the
subsequent
reperfusion
process
can
result
in
myocardial
ischemia–reperfusion
injury
(MIRI).
Mitophagy,
specialized
autophagic
mechanism,
has
consistently
been
implicated
various
disorders.
However,
specific
connection
between
mitophagy
remains
elusive.
This
study
aims
to
elucidate
validate
central
mitophagy-related
genes
MIRI
through
comprehensive
bioinformatics
analysis.
Methods
We
acquired
microarray
expression
profile
dataset
(GSE108940)
from
Gene
Expression
Omnibus
(GEO)
identified
differentially
expressed
(DEGs)
using
GEO2R.
Subsequently,
these
DEGs
were
cross-referenced
database,
differential
nucleotide
sequence
analysis
was
performed
enrichment
Protein–protein
interaction
(PPI)
network
employed
identify
hub
genes,
followed
by
clustering
cytoHubba
MCODE
within
Cytoscape
software.
set
(GSEA)
conducted
on
genes.
Additionally,
Western
blotting,
immunofluorescence,
quantitative
polymerase
chain
reaction
(qPCR)
analyses
patterns
pivotal
rat
model
H9C2
cardiomyocytes.
Results
A
total
2719
61
mitophagy-DEGs
identified,
construction
PPI
network.
HSP90AA1,
RPS27A,
EEF2,
EIF4A1,
EIF2S1,
HIF-1α,
BNIP3
emerged
as
seven
Functional
HIF-1α
yielded
score
9.647,
determined
(MCODE).
In
our
model,
blot
immunofluorescence
confirmed
elevation
BNIP3,
accompanied
notable
increase
ratio
LC3II
LC3I.
qPCR
upregulation
LC3
mRNA
group.
Activation
HIF-1α/BNIP3
pathway
mediates
regulation
degree
thereby
effectively
reducing
apoptosis
Conclusions
among
that
may
play
role
MIRI,
suggesting
correlation
pathogenesis
MIRI.
The
findings
highlight
potential
importance
provide
valuable
insights
into
underlying
mechanisms
therapeutic
targets
further
exploration
future
studies.
Annals of the Rheumatic Diseases,
Год журнала:
2024,
Номер
unknown, С. ard - 225343
Опубликована: Май 8, 2024
Recent
studies
indicate
that
N-acetyltransferase
10
(NAT10)-mediated
ac4C
modification
plays
unique
roles
in
tumour
metastasis
and
immune
infiltration.
This
study
aimed
to
uncover
the
role
of
NAT10-mediated
fibroblast-like
synoviocytes
(FLSs)
functions
synovial
cell
infiltration
rheumatoid
arthritis
(RA).
Cell Death and Disease,
Год журнала:
2025,
Номер
16(1)
Опубликована: Фев. 6, 2025
Abstract
Super-enhancers
(SEs)
are
associated
with
key
genes
that
control
cellular
state
and
cell
identity.
Endoplasmic
reticulum
stress
(ERS)
regulates
epithelial-mesenchymal
transformation
(EMT).
However,
whether
SEs
involved
in
ERS-related
activation
of
EMT
hepatocellular
carcinoma
(HCC)
is
unknown.
In
this
study,
we
identified
17
by
comparing
ERS-HCC
cells
untreated
using
ChIP-seq
RNA-seq.
CRISPR-Cas9
RT-qPCR
CAMP
responsive
element
binding
protein
5
(CREB5)
as
a
target
SE.
Analyses
TCGA
datasets
tissue
arrays
showed
CREB5
mRNA
expression
levels
were
higher
liver
cancer
tissues
than
paired
normal
tissues.
addition,
overexpression
was
poor
prognosis
an
aggressive
phenotype
patients
HCC.
We
also
found
ERS
enhanced
the
CREB5,
upregulation
significantly
increased
proliferation,
migration,
invasion,
promoted
EMT,
but
inhibited
apoptosis.
More
importantly,
several
markers
modulating
CREB5.
Mechanistically,
upregulates
transcription
tenascin-C
(TNC)
directly
to
its
promoter
region,
thereby
promoting
cells.
summary,
our
findings
suggest
promotes
via
SE-mediated
CREB5/TNC
pathway.
This
result
provides
new
direction
for
uncovering
how
foundation
preventing
progression
