PubMed,
Год журнала:
2023,
Номер
13(4), С. 1363 - 1376
Опубликована: Янв. 1, 2023
Epstein-Barr
virus
(EBV)
can
infect
the
majority
of
human
population
with
no
obvious
symptoms
and
is
associated
tumor
development,
although
mechanism
still
largely
unknown.
In
this
study,
we
investigated
role
underlying
EBV
nuclear
antigen
2
(EBNA2)
in
tumorigenesis.
We
found
that
infection
EBNA2
B
lymphocytes
(HBL)
upregulated
expression
activating
transcription
factor
4
(ATF4).
Furthermore,
used
gene
or
knockdown
approach
to
demonstrate
effect
on
redox
balance,
mitochondrial
function,
lipid
metabolism,
cell
proliferation
both
HBL
EBV-transformed
lymphocyte
line
(LCL).
More
importantly,
applied
vivo
xenograft
mouse
model
explore
contribution
ATF4
growth
survival.
Mechanistically,
revealed
exposure
caused
persistent
via
EBNA2-mediated
epigenetic
changes,
which
increased
binding
ability
upstream
stimulating
1
(USF1)
promoter.
activation
cells
modulated
metabolism-related
genes
potentiated
fatty
acid
oxidation
lipogenesis.
Conversely,
either
LCL
suppressed
balance
as
well
inhibited
proliferation.
consistent
these
findings
from
vitro
an
confirmed
SREBP1,
ChREBP,
FAS,
prolonged
animal
Collectively,
study
demonstrates
mediates
tumorigenesis
through
modulation
metabolism;
therefore,
our
provide
a
novel
avenue
for
clinical
treatment
EBV-mediated
cancer.
Redox Biology,
Год журнала:
2024,
Номер
73, С. 103208 - 103208
Опубликована: Май 24, 2024
Recently,
numerous
studies
have
reported
the
interaction
between
senescence
and
oxidative
stress
in
cancer.
However,
there
is
a
lack
of
comprehensive
understanding
precise
mechanisms
involved.
Redox Biology,
Год журнала:
2023,
Номер
60, С. 102626 - 102626
Опубликована: Фев. 2, 2023
Radioresistance
is
the
major
reason
for
failure
of
radiotherapy
in
esophageal
squamous
cell
carcinoma
(ESCC).
Previous
evidence
indicated
that
stanniocalcin
2
(STC2)
participates
various
biological
processes
malignant
tumors.
However,
researches
on
its
effect
radioresistance
cancers
are
limited.
In
this
study,
STC2
was
screened
out
by
RNA-sequencing
and
bioinformatics
analyses
as
a
potential
prognosis
predictor
ESCC
radiosensitivity
then
determined
to
facilitate
radioresistance.
We
found
expression
increased
tissues
compared
adjacent
normal
tissues,
higher
level
associated
with
poor
prognosis.
Also,
mRNA
protein
levels
were
radioresistant
cells
than
their
parental
cells.
Further
investigation
revealed
could
interact
methyltransferase
5
(PRMT5)
activate
PRMT5,
thus
leading
symmetric
dimethylation
histone
H4
Arg
3
(H4R3me2s).
Mechanistically,
can
promote
DDR
through
homologous
recombination
non-homologous
end
joining
pathways
activating
PRMT5.
Meanwhile,
participate
SLC7A11-mediated
ferroptosis
PRMT5-dependent
manner.
Finally,
these
results
validated
vivo
experiments.
These
findings
uncovered
might
be
an
attractive
therapeutic
target
overcome
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Янв. 31, 2024
The
accumulation
of
unfolded
or
misfolded
proteins
in
the
endoplasmic
reticulum
(ER)
causes
ER
stress
and
activates
protein
response
(UPR).
As
an
adaptive
cellular
to
hostile
microenvironments,
such
as
hypoxia,
nutrient
deprivation,
oxidative
stress,
chemotherapeutic
drugs,
UPR
is
activated
diverse
cancer
types
functions
a
dynamic
tumour
promoter
development;
this
role
indicates
that
regulation
can
be
utilized
target
for
treatment.
T-cell
exhaustion
mainly
refers
effector
T
cells
losing
their
expressing
inhibitory
receptors,
leading
immune
evasion
loss
control.
Emerging
evidence
suggests
plays
crucial
exhaustion,
evasion,
resistance
immunotherapy.
In
review,
we
summarize
molecular
basis
activation,
effect
on
emerging
mechanisms
chemotherapy
immunotherapy
resistance,
agents
therapeutics.
An
understanding
therapeutic
will
helpful
identify
new
modalities
Video
Abstract.
Frontiers in Oncology,
Год журнала:
2023,
Номер
13
Опубликована: Сен. 19, 2023
Approximately
15%
of
cancers
exhibit
loss
the
chromosomal
locus
9p21.3
–
genomic
location
tumour
suppressor
gene
CDKN2A
and
methionine
salvage
methylthioadenosine
phosphorylase
(
MTAP
).
A
increases
pool
its
substrate
(MTA),
which
binds
to
inhibits
activity
protein
arginine
methyltransferase
5
(PRMT5).
PRMT5
utilises
universal
methyl
donor
S-adenosylmethionine
(SAM)
methylate
residues
substrates
regulate
their
activity,
notably
histones
transcription.
Recently,
targeting
PRMT5,
or
MAT2A
that
impacts
by
producing
SAM,
has
shown
promise
as
a
therapeutic
strategy
in
oncology,
generating
synthetic
lethality
-negative
cancers.
However,
clinical
development
inhibitors
been
challenging
highlights
need
for
further
understanding
downstream
mediators
drug
effects.
Here,
we
discuss
rationale
methods
MAT2A/PRMT5
axis
cancer
therapy.
We
evaluate
current
limitations
our
mechanism
identify
challenges
must
be
addressed
maximise
potential
these
drugs.
In
addition,
review
literature
defining
effectors
could
determine
sensitivity
inhibition
therefore
present
novel
combination
therapies
may
not
rely
on
with
loss.
Cancers,
Год журнала:
2022,
Номер
14(21), С. 5443 - 5443
Опубликована: Ноя. 5, 2022
Arginine
methylation
is
a
common
post-translational
modification
affecting
protein
activity
and
the
transcription
of
target
genes
when
occurs
on
histone
tails.
There
are
nine
arginine
methyltransferases
(PRMTs)
in
mammals,
divided
into
subgroups
depending
they
form
molecule
arginine.
During
formation
maturation
different
types
blood
cells,
PRMTs
play
central
role
by
controlling
cell
differentiation
at
transcriptional
level.
PRMT
enzymatic
necessary
for
many
cellular
processes
hematological
malignancies,
such
as
activation
cycle
proliferation,
inhibition
apoptosis,
DNA
repair
processes,
RNA
splicing,
methylating
tails’
Chemical
tools
have
been
developed
to
inhibit
tested
several
models
including
primary
samples
from
patients,
xenografts
immunodeficient
mice,
mouse
models,
human
lines.
They
show
significant
effect
reducing
viability
increasing
overall
survival
mice.
PRMT5
inhibitors
strong
therapeutic
potential,
phase
I
clinical
trials
malignancies
that
use
these
molecules
promising
results,
thus,
underlining
useful
cancer
treatment
future.
To
investigate
the
role
of
ALKBH3
in
acute
myeloid
leukemia
(AML),
we
constructed
an
animal
model
xenotransplantation
AML.
Our
study
demonstrated
that
ALKBH3-mediated
m1A
demethylation
inhibits
ferroptosis
KG-1
cells
by
increasing
ATF4
expression,
thus
promoting
development
These
findings
suggest
reducing
expression
may
be
a
potential
strategy
to
mitigate
AML
progression.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Янв. 21, 2025
Aging
is
characterized
by
cellular
degeneration
and
impaired
physiological
functions,
leading
to
a
decline
in
male
sexual
desire
reproductive
capacity.
Oxidative
stress
(OS)
lead
testicular
aging
impairing
the
system,
but
potential
mechanisms
remain
unclear.
In
present
study,
functional
status
of
tissues
from
young
aged
boars
was
compared,
transcriptional
responses
Leydig
cells
(LCs)
hydrogen
peroxide
(H2O2)-induced
senescence
were
explored,
revealing
role
OS
promoting
system.
601
differentially
expressed
genes
(DEGs)
associated
with
OS,
cell
cycle
regulation,
intracellular
processes
identified.
These
DEGs
significantly
enriched
critical
pathways,
including
p53
signaling
pathway,
autophagy,
senescence.
Protein-protein
interaction
(PPI)
network
analysis
unveiled
15
key
related
DNA
replication,
polo-like
kinase
3
(PLK3)
exhibiting
increased
expression
under
OS.
vitro,
PLK3
knockdown
enhanced
viability
antioxidant
capacity
LCs
This
study
deepens
our
understanding
how
respond
provides
new
therapeutic
targets
for
enhancing
resistance
oxidative
damage
tissue
health.
