Protein & Cell,
Год журнала:
2024,
Номер
15(10), С. 744 - 765
Опубликована: Март 13, 2024
Coactivator-associated
arginine
methyltransferase
1
(CARM1)
promotes
the
development
and
metastasis
of
estrogen
receptor
alpha
(ERα)-positive
breast
cancer.
The
function
CARM1
in
triple-negative
cancer
(TNBC)
is
still
unclear
requires
further
exploration.
Here,
we
report
that
proliferation,
epithelial-mesenchymal
transition,
stemness
TNBC.
upregulated
multiple
cancers
its
expression
correlates
with
progression.
Genome-wide
analysis
showed
recruited
by
hypoxia-inducible
factor-1
subunit
(HIF1A)
occupy
promoters
CDK4,
Cyclin
D1,
β-Catenin,
HIF1A,
MALAT1,
SIX1
critically
involved
cell
cycle,
HIF-1
signaling
pathway,
Wnt
VEGF
thereby
modulating
proliferation
invasion
TNBC
cells.
We
demonstrated
physically
associated
directly
interacts
HIF1A.
Moreover,
found
ellagic
acid,
an
inhibitor
CARM1,
can
suppress
inhibiting
CDK4
expression.
Our
research
has
determined
molecular
basis
carcinogenesis
effective
natural
inhibitor,
which
may
provide
new
ideas
drugs
for
therapy.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Апрель 10, 2023
Abstract
Vascular
complications
of
diabetes
pose
a
severe
threat
to
human
health.
Prevention
and
treatment
protocols
based
on
single
vascular
complication
are
no
longer
suitable
for
the
long-term
management
patients
with
diabetes.
Diabetic
panvascular
disease
(DPD)
is
clinical
syndrome
in
which
vessels
various
sizes,
including
macrovessels
microvessels
cardiac,
cerebral,
renal,
ophthalmic,
peripheral
systems
diabetes,
develop
atherosclerosis
as
common
pathology.
Pathological
manifestations
DPDs
usually
manifest
macrovascular
atherosclerosis,
well
microvascular
endothelial
function
impairment,
basement
membrane
thickening,
microthrombosis.
Cardiac,
microangiopathy
coexist
microangiopathy,
while
renal
retinal
predominantly
microangiopathic.
The
following
associations
exist
between
DPDs:
numerous
similar
molecular
mechanisms,
risk-predictive
relationships
diseases.
Aggressive
glycemic
control
combined
early
comprehensive
intervention
key
prevention
treatment.
In
addition
widely
recommended
metformin,
glucagon-like
peptide-1
agonist,
sodium-glucose
cotransporter-2
inhibitors,
latest
aldose
reductase
peroxisome
proliferator-activated
receptor-γ
agonizts,
glucokinases
mitochondrial
energy
modulators,
etc.
under
active
development.
proposed
obtain
more
systematic
care
requires
center
focusing
This
would
leverage
advantages
cross-disciplinary
approach
achieve
better
integration
pathogenesis
therapeutic
evidence.
Such
strategy
confer
benefits
promote
development
DPD
discipline.
Genes & Development,
Год журнала:
2022,
Номер
36(5-6), С. 278 - 293
Опубликована: Март 1, 2022
DNA
repair
and
damage
signaling
pathways
are
critical
for
the
maintenance
of
genomic
stability.
Defects
contribute
to
tumorigenesis,
but
also
render
cancer
cells
vulnerable
reliant
on
remaining
activities.
Here,
we
review
major
classes
defects
in
cancer,
instability
that
they
give
rise
to,
therapeutic
strategies
exploit
resulting
vulnerabilities.
Furthermore,
discuss
impacts
both
targeted
therapy
immunotherapy,
highlight
emerging
principles
targeting
therapy.
Cell,
Год журнала:
2023,
Номер
186(21), С. 4475 - 4495
Опубликована: Окт. 1, 2023
ADP-ribosylation
is
a
ubiquitous
modification
of
biomolecules,
including
proteins
and
nucleic
acids,
that
regulates
various
cellular
functions
in
all
kingdoms
life.
The
recent
emergence
new
technologies
to
study
has
reshaped
our
understanding
the
molecular
mechanisms
govern
establishment,
removal,
recognition
this
modification,
as
well
its
impact
on
organismal
function.
These
advances
have
also
revealed
intricate
involvement
human
physiology
pathology
enormous
potential
their
manipulation
holds
for
therapy.
In
review,
we
present
state-of-the-art
findings
covering
work
structural
biology,
biochemistry,
cell
clinical
aspects
ADP-ribosylation.
Mutation
signatures
associated
with
apolipoprotein
B
mRNA
editing
catalytic
polypeptide-like
3A/B
(APOBEC3A/B)
cytidine
deaminases
are
prevalent
across
cancers,
implying
their
roles
as
mutagenic
drivers
during
tumorigenesis
and
tumor
evolution.
APOBEC3A
(A3A)
expression
induces
DNA
replication
stress
increases
the
cellular
dependency
on
ataxia
telangiectasia
Rad3-related
(ATR)
kinase
for
survival.
Nonetheless,
how
A3A
remains
unclear.
We
show
that
without
slowing
forks.
find
single-stranded
(ssDNA)
gaps
through
PrimPol-mediated
repriming.
A3A-induced
ssDNA
repaired
by
multiple
pathways
involving
ATR,
RAD51,
translesion
synthesis.
Both
ATR
inhibition
trapping
of
poly(ADP-ribose)
polymerase
(PARP)
PARP
inhibitor
impair
repair
gaps,
preferentially
killing
A3A-expressing
cells.
When
used
in
combination,
inhibitors
selectively
kill
cells
synergistically
a
manner
dependent
PrimPol-generated
gaps.
Thus,
arises
from
which
confer
therapeutic
vulnerability
to
gap-targeted
inhibitors.
Genes & Development,
Год журнала:
2021,
Номер
35(17-18), С. 1271 - 1289
Опубликована: Авг. 12, 2021
PARP
inhibitor
(PARPi)
is
widely
used
to
treat
BRCA1/2-deficient
tumors,
but
why
PARPi
more
effective
than
other
DNA-damaging
drugs
unclear.
Here,
we
show
that
generates
DNA
double-strand
breaks
(DSBs)
predominantly
in
a
trans
cell
cycle
manner.
During
the
first
S
phase
after
exposure,
induces
single-stranded
(ssDNA)
gaps
behind
replication
forks.
By
trapping
on
DNA,
prevents
completion
of
gap
repair
until
next
phase,
leading
collisions
forks
with
ssDNA
and
surge
DSBs.
In
second
cells
are
unable
suppress
origin
firing
through
ATR,
resulting
continuous
synthesis
Furthermore,
cannot
recruit
RAD51
collapsed
Thus,
DSBs
progressively
gaps,
fail
slow
down
over
multiple
cycles,
explaining
unique
efficacy
cells.
