Cancer Science,
Год журнала:
2023,
Номер
114(5), С. 1912 - 1928
Опубликована: Янв. 13, 2023
Invasive
micropapillary
carcinoma
(IMPC)
is
a
special
histopathological
subtype
of
breast
cancer.
Clinically,
IMPC
exhibits
higher
incidence
lymphovascular
invasion
and
lymph
node
metastasis
compared
with
that
invasive
ductal
(IDC),
the
most
common
type.
However,
metabolic
characteristics
related
mechanisms
underlying
malignant
biological
behaviors
are
unknown.
We
performed
large-scale
targeted
metabolomics
analysis
on
resected
tumors
obtained
from
chemotherapy-naïve
(n
=
25)
IDC
26)
patients
to
investigate
alterations,
we
integrated
mass
spectrometry
analysis,
RNA
sequencing,
ChIP-sequencing
data
elucidate
potential
molecular
mechanisms.
The
revealed
distinct
profiles
between
IDC.
For
patients,
metabolomic
profile
was
characterized
by
significantly
high
levels
arginine
methylation
marks,
protein
methyltransferase
3
(PRMT3)
identified
as
critical
regulator
catalyzed
formation
these
marks.
Notably,
overexpression
PRMT3
an
independent
risk
factor
for
poor
prognosis.
Furthermore,
demonstrated
key
cancer
cell
proliferation
both
in
vitro
vivo,
treatment
preclinical
inhibitor
decreased
xenograft
tumorigenic
capacity.
Mechanistically,
regulated
endoplasmic
reticulum
(ER)
stress
signaling
pathway
facilitating
histone
H4
asymmetric
dimethylation
(H4R3me2a),
which
may
endow
cells
great
proliferative
metastatic
Our
findings
highlight
importance
regulating
behavior
suggest
small-molecule
inhibitors
activity
might
be
promising
treatments.
Protein
posttranslational
modifications
(PTMs)
refer
to
the
breaking
or
generation
of
covalent
bonds
on
backbones
amino
acid
side
chains
proteins
and
expand
diversity
proteins,
which
provides
basis
for
emergence
organismal
complexity.
To
date,
more
than
650
types
protein
modifications,
such
as
most
well-known
phosphorylation,
ubiquitination,
glycosylation,
methylation,
SUMOylation,
short-chain
long-chain
acylation
redox
irreversible
have
been
described,
inventory
is
still
increasing.
By
changing
conformation,
localization,
activity,
stability,
charges,
interactions
with
other
biomolecules,
PTMs
ultimately
alter
phenotypes
biological
processes
cells.
The
homeostasis
important
human
health.
Abnormal
may
cause
changes
in
properties
loss
functions,
are
closely
related
occurrence
development
various
diseases.
In
this
review,
we
systematically
introduce
characteristics,
regulatory
mechanisms,
functions
health
addition,
therapeutic
prospects
diseases
by
targeting
associated
enzymes
also
summarized.
This
work
will
deepen
understanding
promote
discovery
diagnostic
prognostic
markers
drug
targets
European Journal of Internal Medicine,
Год журнала:
2023,
Номер
114, С. 15 - 22
Опубликована: Июнь 3, 2023
Epigenetics
is
a
rapidly
growing
field
of
biology
that
studies
the
changes
in
gene
expression
are
not
due
to
alterations
DNA
sequence
but
rather
chemical
modifications
and
its
associated
proteins.
Epigenetic
mechanisms
can
profoundly
influence
expression,
cell
differentiation,
tissue
development,
disease
susceptibility.
Understanding
epigenetic
essential
elucidate
underlying
increasingly
recognized
role
environmental
lifestyle
factors
health
intergenerational
transmission
phenotypes.
Recent
suggest
epigenetics
may
be
critical
various
diseases,
from
cardiovascular
cancer
neurodevelopmental
neurodegenerative
disorders.
potentially
reversible
could
provide
new
therapeutic
avenues
for
treating
these
diseases
using
modulators.
Moreover,
insight
into
pathogenesis
biomarkers
diagnosis
risk
stratification.
Nevertheless,
interventions
have
potential
unintended
consequences
lead
increased
risks
unexpected
outcomes,
such
as
adverse
drug
reactions,
developmental
abnormalities,
cancer.
Therefore,
rigorous
minimize
with
therapies
develop
safe
effective
improving
human
health.
This
article
provides
synthetic
historical
view
origin
some
most
relevant
achievements.
Cell Reports,
Год журнала:
2022,
Номер
38(13), С. 110582 - 110582
Опубликована: Март 1, 2022
Despite
the
success
of
immune
checkpoint
inhibitor
(ICI)
therapy
for
cancer,
resistance
and
relapse
are
frequent.
Combination
therapies
expected
to
enhance
response
rates
overcome
this
resistance.
Herein,
we
report
that
combining
PRMT7
inhibition
with
ICI
induces
a
strong
anti-tumor
T
cell
immunity
restrains
tumor
growth
in
vivo
by
increasing
infiltration.
PRMT7-deficient
B16.F10
melanoma
exhibits
increased
expression
genes
interferon
pathway,
antigen
presentation,
chemokine
signaling.
deficiency
or
SGC3027
results
reduced
DNMT
expression,
loss
DNA
methylation
regulatory
regions
endogenous
retroviral
elements
(ERVs)
causing
their
expression.
cells
increase
RIG-I
MDA5
reduction
H4R3me2s
repressive
histone
mark
at
gene
promoters.
Our
findings
identify
as
RIG-I,
MDA5,
ERV-double-stranded
RNA
(dsRNA)
ligands,
facilitating
escape
restrain
growth.
Molecular Medicine,
Год журнала:
2023,
Номер
29(1)
Опубликована: Июль 6, 2023
Abstract
The
metabolism
of
glucose
and
lipids
is
essential
for
energy
production
in
the
body,
dysregulation
metabolic
pathways
these
molecules
implicated
various
acute
chronic
diseases,
such
as
type
2
diabetes,
Alzheimer’s
disease,
atherosclerosis
(AS),
obesity,
tumor,
sepsis.
Post-translational
modifications
(PTMs)
proteins,
which
involve
addition
or
removal
covalent
functional
groups,
play
a
crucial
role
regulating
protein
structure,
localization
function,
activity.
Common
PTMs
include
phosphorylation,
acetylation,
ubiquitination,
methylation,
glycosylation.
Emerging
evidence
indicates
that
are
significant
modulating
lipid
by
modifying
key
enzymes
proteins.
In
this
review,
we
summarize
current
understanding
regulatory
mechanisms
metabolism,
with
focus
on
their
involvement
disease
progression
associated
aberrant
metabolism.
Furthermore,
discuss
future
prospects
PTMs,
highlighting
potential
gaining
deeper
insights
into
related
diseases.
Cell Death and Disease,
Год журнала:
2023,
Номер
14(10)
Опубликована: Окт. 9, 2023
Overcoming
distant
metastasis
stands
as
a
paramount
challenge
in
enhancing
the
outcomes
of
breast
cancer
treatments.
Thus,
delving
deeper
into
comprehending
intricate
mechanisms
underlying
becomes
imperative,
offering
potential
avenues
for
pioneering
therapeutic
approaches.
PRMT6,
an
arginine
N-methyltransferase,
possesses
ability
to
methylate
both
histone
and
non-histone
proteins.
It
has
been
reported
that
methylation
proteins
impacts
their
cellular
localization,
stability,
activation,
consequently
influencing
tumor
progression.
However,
extent
which
PRMT6-mediated
protein
influences
cell
metastasis,
particularly
context
cancer,
remains
elusive.
In
this
study,
we
established
PRMT6
exerted
positive
regulatory
influence
on
through
vivo
vitro
experiments.
Mechanistically,
innovatively
revealed
asymmetrically
di-methylated
STAT3
at
729
(STAT3
R729me2a).
This
modification
proved
indispensable
STAT3's
membrane
its
interaction
with
JAK2,
Y705
phosphorylation,
PRMT6-driven
metastasis.
From
clinical
perspective,
unearthed
promising
R729me2a
robust
prognostic
marker
predicting
overall
survival
time
patients.
terms
intervention,
demonstrated
significant
capability
inhibitor,
EPZ020411,
curtail
vitro.
sum,
our
study
unveils
pivotal
biological
role
underscores
prospective
utility
inhibitors
effective
strategies
against
STAT3-driven
metastatic
cancer.
Drug Resistance Updates,
Год журнала:
2023,
Номер
72, С. 101016 - 101016
Опубликована: Ноя. 3, 2023
Drug
resistance
remains
a
major
challenge
in
cancer
treatment,
necessitating
the
development
of
novel
strategies
to
overcome
it.
Protein
arginine
methyltransferases
(PRMTs)
are
enzymes
responsible
for
epigenetic
methylation,
which
regulates
various
biological
and
pathological
processes,
as
result,
they
attractive
therapeutic
targets
overcoming
anti-cancer
drug
resistance.
The
ongoing
small
molecules
targeting
PRMTs
has
resulted
generation
chemical
probes
modulating
most
facilitated
clinical
treatment
advanced
oncology
targets,
including
PRMT1
PRMT5.
In
this
review,
we
summarize
mechanisms
underlying
protein
methylation
roles
specific
driving
Furthermore,
highlight
potential
implications
PRMT
inhibitors
decreasing
promote
formation
maintenance
drug-tolerant
cells
via
several
mechanisms,
altered
efflux
transporters,
autophagy,
DNA
damage
repair,
stem
cell-related
function,
epithelial-mesenchymal
transition,
disordered
tumor
microenvironment.
Multiple
preclinical
trials
have
demonstrated
that
inhibitors,
particularly
PRMT5
can
sensitize
drugs,
chemotherapeutic,
targeted
therapeutic,
immunotherapeutic
agents.
Combining
with
existing
will
be
promising
approach
enhanced
knowledge
complex
functions
guide
future
may
help
identify
new
indications.
Chemical Reviews,
Год журнала:
2024,
Номер
124(5), С. 2805 - 2838
Опубликована: Фев. 19, 2024
Post-translational
modifications
(PTMs)
endow
proteins
with
new
properties
to
respond
environmental
changes
or
growth
needs.
With
the
development
of
advanced
proteomics
techniques,
hundreds
distinct
types
PTMs
have
been
observed
in
a
wide
range
from
bacteria,
archaea,
and
eukarya.
To
identify
roles
these
PTMs,
scientists
applied
various
approaches.
However,
high
dynamics,
low
stoichiometry,
crosstalk
between
make
it
almost
impossible
obtain
homogeneously
modified
for
characterization
site-specific
effect
individual
PTM
on
target
proteins.
solve
this
problem,
genetic
code
expansion
(GCE)
strategy
has
introduced
into
field
studies.
Instead
modifying
after
translation,
GCE
incorporates
amino
acids
during
thus
generating
site-specifically
at
positions.
In
review,
we
summarize
systems
orthogonal
translation
installation
PTMs.
Cancer Communications,
Год журнала:
2024,
Номер
44(6), С. 601 - 636
Опубликована: Май 7, 2024
Abstract
Significant
developments
in
cancer
treatment
have
been
made
since
the
advent
of
immune
therapies.
However,
there
are
still
some
patients
with
malignant
tumors
who
do
not
benefit
from
immunotherapy.
Tumors
without
immunogenicity
called
“cold”
which
unresponsive
to
immunotherapy,
and
opposite
“hot”
tumors.
Immune
suppressive
cells
(ISCs)
refer
can
inhibit
response
such
as
tumor‐associated
macrophages
(TAMs),
myeloid‐derived
suppressor
(MDSCs),
regulatory
T
(Treg)
so
on.
The
more
ISCs
infiltrated,
weaker
tumor,
showing
characteristics
tumor.
dysfunction
tumor
microenvironment
(TME)
may
play
essential
roles
insensitive
therapeutic
reaction.
Previous
studies
found
that
epigenetic
mechanisms
an
important
role
regulation
ISCs.
Regulating
be
a
new
approach
transforming
into
Here,
we
focused
on
function
TME
discussed
how
epigenetics
is
involved
regulating
In
addition,
summarized
by
drugs
convert
immunotherapy‐insensitive
immunotherapy‐sensitive
would
innovative
tendency
for
future
immunotherapy