Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Май 1, 2025
Histone
modifications,
including
methylation,
acetylation,
lactylation,
phosphorylation,
ubiquitination,
SUMOylation,
ADP-ribosylation,
and
crotonylation,
critically
regulate
tumor-associated
macrophages
(TAMs)
polarization
by
modulating
gene
expression
functional
states.
Reprogramming
TAMs
from
M2
to
M1
phenotypes
through
epigenetic
targeting
has
emerged
as
a
promising
strategy
enhance
anti-tumor
immunity
improve
the
efficacy
of
cancer
immunotherapy.
This
review
explores
role
histone
modifications
in
TAM
biology,
their
interplay
with
metabolic
reprogramming,
opportunities
challenges
developing
epigenetic-based
therapies
advance
Journal of Nanobiotechnology,
Год журнала:
2025,
Номер
23(1)
Опубликована: Фев. 28, 2025
The
mean
survival
of
metastatic
lung
adenocarcinoma
is
less
than
1
year,
highlighting
the
urgent
need
to
understand
mechanisms
underlying
its
high
mortality
rate.
role
Extracellular
vesicles
(EVs)
in
facilitating
interactions
between
cancer
cells
and
microenvironment
has
garnered
increasing
attention.
Previous
studies
on
EVs
metastasis
have
been
primarily
focused
cell-derived
modulating
functions
stromal
cells.
However,
whether
stem
(CSCs)
can
alter
properties
non-CSC
cells,
EV
crosstalk
mediate
such
interaction,
not
demonstrated
prior
this
report.
In
present
study,
we
integrated
multi-omics
sequencing
public
database
analysis
with
experimental
validation
demonstrate,
for
first
time,
exosomal
Mir100hg,
derived
from
CSCs,
could
enhance
potential
non-CSCs
both
vitro
vivo.
Mechanistically,
HNRNPF
HNRNPA2B1
directly
binds
trafficking
via
exosomes
non-CSCs.
non-CSCs,
Mir100hg
upregulates
ALDOA
expression,
subsequently
leading
elevated
lactate
production.
Consequently,
increased
levels
H3K14
lactylation
by
2.5-fold
promote
transcription
169
metastasis-related
genes.
This
cascade
events
ultimately
results
enhanced
ALDOA-driven
glycolysis
histone
lactylation-mediated
We
delineated
a
complex
regulatory
network
utilized
CSCs
transfer
their
activity
through
providing
new
mechanistic
insights
into
communication
these
two
heterogeneous
tumor
cell
populations.
These
provide
novel
therapeutic
targets
cancer,
including
HNRNPF/HNRNPA2B1-mediated
pathway,
advancing
our
understanding
CSC-mediated
while
suggesting
promising
strategies
clinical
intervention.
Theranostics,
Год журнала:
2025,
Номер
15(5), С. 1787 - 1821
Опубликована: Янв. 2, 2025
Lactate
is
an
indispensable
substance
in
various
cellular
physiological
functions
and
plays
regulatory
roles
different
aspects
of
energy
metabolism
signal
transduction.
Lactylation
(Kla),
a
key
pathway
through
which
lactate
exerts
its
functions,
has
been
identified
as
novel
posttranslational
modification
(PTM).
Research
indicates
that
Kla
essential
balancing
mechanism
variety
organisms
involved
many
biological
processes
pathways.
closely
related
to
disease
development
represents
potential
important
new
drug
target.
In
line
with
existing
reports,
we
searched
for
newly
discovered
sites
on
histone
nonhistone
proteins;
reviewed
the
mechanisms
(particularly
focusing
enzymes
directly
reversible
regulation
Kla,
including
"writers"
(modifying
enzymes),
"readers"
(modification-binding
"erasers"
(demodifying
enzymes);
summarized
crosstalk
between
PTMs
help
researchers
better
understand
widespread
distribution
diverse
functions.
Furthermore,
considering
"double-edged
sword"
role
both
pathological
contexts,
this
review
highlights
"beneficial"
states
(energy
metabolism,
inflammatory
responses,
cell
fate
determination,
development,
etc.)
"detrimental"
pathogenic
or
inducive
effects
processes,
particularly
malignant
tumors
complex
nontumor
diseases.
We
also
clarify
molecular
health
disease,
discuss
feasibility
therapeutic
Finally,
describe
detection
technologies
their
applications
diagnosis
clinical
settings,
aiming
provide
insights
treatment
diseases
accelerate
translation
from
laboratory
research
practice.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
During
skeletal
growth,
there
is
an
increased
secretion
of
lactate
by
glycolytic
nucleus
pulposus
(NP)
cells
the
intervertebral
disc.
To
investigate
role
this
anion,
we
generated
annulus
fibrosus
(AF)
and
endplate
(EP)
specific
Mct1
cKO
(
Slc16a1
Col2CreERT2
)
mice.
Histological
spatial
transcriptomic
studies
indicated
significant
disc
degeneration
in
,
characterized
NP
cell
loss
delayed
EP
maturation.
Metabolic
assays
showed
that
while
AF
were
glycolytic,
chondrocytes
readily
metabolized
lactate.
In
cells,
promoted
protein,
H3K18
lactylation,
implying
epigenetic
programming.
These
findings
suggest
NP-derived
promotes
cartilage
transdifferentiation
into
subchondral
bone,
its
absence,
continued
glucose
consumption
persistent
reduces
availability
to
likely
contributing
tissue
degeneration.
This
study
provides
first
vivo
evidence
metabolic
coupling
between
essential
for
growth
health.
Lipids in Health and Disease,
Год журнала:
2025,
Номер
24(1)
Опубликована: Фев. 25, 2025
Elevated
incidence
of
metabolic
disorders
has
been
reported
worldwide
in
the
recent
decade,
highlighting
need
for
developing
efficient
therapies.
These
diseases
result
from
a
complex
interplay
various
factors
that
contribute
to
disease
progression,
complications,
and
resistance
current
treatment
options.
Acetyl-CoA
Synthetase
Short
Chain
Family
Member
2
(ACSS2)
is
nucleo-cytosolic
enzyme
with
both
lipogenic
regulatory
roles.
Studies
on
ACSS2
have
shown
it
involved
pathways
commonly
dysregulated
disorders,
leading
fat
deposition
disrupted
cellular
signaling.
Although
multiple
studies
suggested
role
rewiring
during
tumorigenesis,
few
examined
its
involvement
pathophysiology
diseases.
Recent
evidence
indicates
may
pathogenesis
making
examination
great
interest
potentially
aiding
development
new
therapeutic
strategies.
The
objective
this
review
summarize
understanding
ACSS2's
potential
as
target.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 28, 2025
Metabolism
and
post-translational
modifications
(PTMs)
are
intrinsically
linked
the
number
of
identified
metabolites
that
can
covalently
modify
proteins
continues
to
increase.
This
metabolism/PTM
crosstalk
is
especially
true
for
lactate,
product
anaerobic
metabolism
following
glycolysis.
Lactate
forms
an
amide
bond
with
ε-amino
group
lysine,
a
modification
known
as
lysine
lactylation,
or
Kla.
Multiple
independent
mechanisms
have
been
proposed
in
formation
Kla,
including
p300/CBP-dependent
transfer
from
lactyl-CoA,
via
high-energy
intermediate
lactoylglutathione
species
non-enzymatically
lactylates
proteins,
several
enzymes
reported
lactyl
transferase
capability.
We
recently
discovered
class
I
histone
deacetylases
(HDACs)
1,
2,
3
all
reverse
their
canonical
chemical
reaction
catalyze
β-hydroxybutyrylation.
Here
we
tested
hypothesis
HDACs
also
Kla
formation.
Using
biochemical,
pharmacological,
genetic
approaches,
found
HDAC-catalyzed
lactylation
accounts
majority
cells.
Dialysis
experiments
confirm
this
reversible
depends
on
lactate
concentration.
directly
quantified
intracellular
lactyl-CoA
abundance
be
uncoupled
levels.
Therefore,
propose
model
which
formed
through
enzymatic
addition
by
3.
