ABSTRACT
Epigenetic
regulation
in
disease
development
has
been
witnessed
within
this
decade.
RNA
methylation
is
the
predominant
form
of
epigenetic
regulation,
and
most
prevalent
modification
N6‐methyladenosine
(m
6
A).
Recently,
emerged
as
a
potential
target
for
treatment.
posttranscriptional
gene
expression
that
involved
both
physiological
pathological
processes.
Evidence
suggests
m
A
significantly
affects
metabolism,
its
abnormal
changes
have
observed
variety
diseases.
Metabolic
diseases
are
series
caused
by
metabolic
processes
body,
common
include
diabetes
mellitus,
obesity,
nonalcoholic
fatty
liver
disease,
etc.;
although
pathogenesis
these
differs
from
each
other
to
current
understanding,
recent
studies
suggested
pivotal
role
modulating
diseases,
A‐based
drug
on
agenda.
This
paper
reviewed
understanding
hoping
provide
systematic
information
those
area.
Liver
cancer
is
the
third
leading
cause
of
cancer-related
deaths
and
ranks
as
sixth
most
prevalent
type
globally.
NAFLD
or
metabolic
dysfunction-associated
steatotic
liver
disease,
its
more
severe
manifestation,
NASH
steatohepatitis
(MASH),
pose
a
significant
global
health
concern,
affecting
approximately
20%-25%
population.
The
increased
prevalence
disease
MASH
parallel
to
increasing
rates
obesity-associated
diseases,
including
2
diabetes,
insulin
resistance,
fatty
diseases.
can
progress
MASH-related
HCC
(MASH-HCC)
in
about
2%
cases
each
year,
influenced
by
various
factors
such
genetic
mutations,
carcinogen
exposure,
immune
microenvironment,
microbiome.
MASH-HCC
exhibits
distinct
molecular
characteristics
compared
other
causes
affects
both
men
women
equally.
management
early
intermediate-stage
typically
involves
surgery
locoregional
therapies,
while
advanced
treated
with
systemic
anti-angiogenic
therapies
checkpoint
inhibitors.
In
this
comprehensive
review,
we
consolidate
previous
research
findings
also
providing
current
insights
into
intricate
processes
underlying
development.
We
delve
MASH-HCC-associated
variations
somatic
progression
models,
multiomics
analysis,
immunological
microenvironmental
impacts,
discuss
targeted/combined
overcome
evasion
biomarkers
recognize
treatment
responders.
By
furthering
our
comprehension
mechanisms
MASH-HCC,
goal
catalyze
advancement
potent
strategies,
ultimately
enhanced
patient
outcomes.
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)
encompasses
a
wide
spectrum
of
injuries,
ranging
from
hepatic
steatosis,
metabolic
steatohepatitis
(MASH),
fibrosis,
cirrhosis
to
MASLD-associated
hepatocellular
carcinoma
(MASLD-HCC).
Recent
studies
have
highlighted
the
bidirectional
impacts
between
host
genetics/epigenetics
and
gut
microbial
community.
Host
genetics
influence
composition
microbiome,
while
microbiota
their
derived
metabolites
can
induce
epigenetic
modifications
affect
development
MASLD.
The
exploration
intricate
relationship
microbiome
genetic/epigenetic
makeup
is
anticipated
yield
promising
avenues
for
therapeutic
interventions
targeting
MASLD
its
associated
conditions.
In
this
review,
we
summarise
effects
alterations
in
MASLD-HCC.
We
further
discuss
research
findings
demonstrating
genetics/epigenetics,
emphasising
significance
interconnection
prevention
treatment.
Gut,
Год журнала:
2024,
Номер
73(12), С. 2023 - 2036
Опубликована: Май 13, 2024
Squalene
epoxidase
(SQLE)
promotes
metabolic
dysfunction-associated
steatohepatitis-associated
hepatocellular
carcinoma
(MASH-HCC),
but
its
role
in
modulating
the
tumour
immune
microenvironment
MASH-HCC
remains
unclear.
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.
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Фев. 28, 2025
M6A
modification
is
one
of
the
most
common
regulatory
mechanisms
gene
expression
in
eukaryotic
cells,
influencing
processes
such
as
RNA
splicing,
degradation,
stability,
and
protein
translation.
Studies
have
shown
that
m6A
methylation
closely
associated
with
tumorigenesis
progression,
it
plays
a
key
role
tumor
immune
responses.
participates
regulating
differentiation
maturation
well
related
anti-tumor
In
microenvironment,
can
also
affect
cell
recruitment,
activation,
polarization,
thereby
promoting
or
inhibiting
proliferation
metastasis,
reshaping
microenvironment.
recent
years,
immunotherapies
for
tumors,
checkpoint
inhibitors
adoptive
immunotherapy,
been
increasingly
applied
clinical
settings,
achieving
favorable
outcomes.
Targeting
modifications
to
modulate
system,
using
small-molecule
target
dysregulated
factors
inducing
reprogramming,
enhance
responses
strengthen
recognition
cytotoxicity
against
cells.
represents
new
direction
immunotherapy
promising
potential.
This
review
discusses
on
cells
explores
strategies
immunotherapy.
Science China Life Sciences,
Год журнала:
2024,
Номер
67(10), С. 2105 - 2119
Опубликована: Май 27, 2024
Abstract
Non-alcoholic
fatty
liver
disease
(NAFLD)
has
emerged
as
a
prominent
global
health
concern
associated
with
high
risk
of
metabolic
syndrome,
and
impacted
substantial
segment
the
population.
The
spectrum
ranges
from
simple
to
non-alcoholic
steatohepatitis
(NASH),
which
can
progress
cirrhosis
hepatocellular
carcinoma
(HCC)
is
increasingly
becoming
prevalent
indication
for
transplantation.
existing
therapeutic
options
NAFLD,
NASH,
HCC
are
limited,
underscoring
urgent
need
innovative
treatment
strategies.
Insights
into
gene
expression,
particularly
RNA
modifications
such
N
6
methyladenosine
(m
A),
hold
promising
avenues
interventions.
These
play
integral
roles
in
metabolism
cellular
functions,
encompassing
entire
NAFLD-NASH-HCC
progression.
This
review
will
encompass
recent
insights
on
diverse
modifications,
including
m
A,
pseudouridine
(ψ),
1
-methyladenosine
5-methylcytidine
5
C)
across
various
species.
It
uncover
their
significance
crucial
aspects
steatosis,
inflammation,
fibrosis,
tumorigenesis.
Furthermore,
prospective
research
directions
implications
be
explored,
advancing
our
comprehensive
understanding
intricate
interconnected
nature
these
pathological
conditions.
Abstract
The
N6‐methyladenosine
(m6A)
RNA
modification
has
gained
significant
prominence
as
a
new
layer
of
regulatory
mechanism
that
governs
gene
expression.
Over
the
past
decade,
various
m6A
regulators
responsible
for
introducing,
eliminating,
and
recognising
methylation
have
been
identified.
Notably,
these
often
exhibit
altered
expression
patterns
in
cancer,
occasionally
offering
prognostic
value.
Nonetheless,
complex
roles
human
cancer
pathology
remain
enigmatic,
with
conflicting
outcomes
reported
different
studies.In
recent
years,
multitude
inhibitors
activators
targeting
reported.
Several
compounds
demonstrated
promising
efficacy
both
vitro
vivo
models.
These
findings
collectively
underscore
dynamic
landscape
regulation
biology,
revealing
its
potential
therapeutic
target
indicator.
