Journal of Inflammation Research,
Год журнала:
2024,
Номер
Volume 17, С. 10397 - 10419
Опубликована: Дек. 1, 2024
Background:
The
ubiquitin-proteasome
system
(UPS)
is
vital
for
protein
quality
control
and
its
dysregulation
linked
to
diseases,
including
cancer.
Targeting
the
UPS
becoming
a
promising
approach
in
cancer
therapy.
However,
role
of
modulation
thyroid
carcinoma
(THCA)
remains
be
fully
elucidated.
Methods:
Initially,
we
utilized
data
from
Cancer
Genome
Atlas
(TCGA)
database
employ
weighted
gene
co-expression
network
analysis
(WGCNA)
with
LASSO
regression
develop
prognostic
model
core
genes
implicated
THCA.
Subsequently,
stratified
THCA
training
set
into
two
distinct
subtypes
based
on
score
(UPS-PMS)
characteristics.
Key
within
were
then
subjected
functional
analysis,
immunotherapy
evaluation,
drug
sensitivity
studies.
Results:
We
delineated
comprising
six
genes,
which
subsequently
demonstrated
was
capable
forecasting
patient
prognosis.
Moreover,
our
findings
indicated
substantial
correlation
between
UPS-PMS
immune
microenvironmental
factors,
notably
negative
myeloid
cells
potential
influence
Th1
Th2
ratio.
Especially,
observed
significant
association
high
an
immunosuppressive
microenvironment.
Then,
elucidated
biological
distinctions
among
various
sample
subtypes,
highlighting
that
cluster_1
subtype
associated
unfavorable
Of
note,
KCNA1
identified
as
pivotal
framework.
constructed
three-tiered
regulatory
centered
KCNA1-related
competing
endogenous
RNA
(ceRNA).
Furthermore,
results
suggested
has
target
immunotherapeutic
strategies.
Concurrently,
analyses
expression
promoted
gemcitabine
resistance
patients,
while
knockdown
increased
gemcitabine.
Conclusion:
In
conclusion,
developed
novel
UPS-based
THCA,
key
KCNA1,
assessed
sensitivity,
revealing
new
therapeutic
targets.
Keywords:
system,
carcinoma,
model,
microenvironment,
Cancers,
Год журнала:
2024,
Номер
16(13), С. 2478 - 2478
Опубликована: Июль 7, 2024
The
rise
of
drug
resistance
in
cancer
cells
presents
a
formidable
challenge
modern
oncology,
necessitating
the
exploration
innovative
therapeutic
strategies.
This
review
investigates
latest
advancements
overcoming
mechanisms
employed
by
cells,
focusing
on
emerging
modalities.
intricate
molecular
insights
into
resistance,
including
genetic
mutations,
efflux
pumps,
altered
signaling
pathways,
and
microenvironmental
influences,
are
discussed.
Furthermore,
promising
avenues
offered
targeted
therapies,
combination
treatments,
immunotherapies,
precision
medicine
approaches
highlighted.
Specifically,
synergistic
effects
combining
traditional
cytotoxic
agents
with
molecularly
inhibitors
to
circumvent
pathways
examined.
Additionally,
evolving
landscape
immunotherapeutic
interventions,
immune
checkpoint
adoptive
cell
is
explored
terms
bolstering
anti-tumor
responses
evasion
mechanisms.
Moreover,
significance
biomarker-driven
strategies
for
predicting
monitoring
treatment
underscored,
thereby
optimizing
outcomes.
For
future
direction
paradigms,
current
focused
prevailing
challenges
improving
patient
outcomes,
through
an
integrative
analysis
these
Cancer-associated
fibroblasts
(CAFs)
are
a
diverse
stromal
cell
population
within
the
tumour
microenvironment,
where
they
play
fundamental
roles
in
cancer
progression
and
patient
prognosis.
Multiple
lines
of
evidence
have
identified
that
CAFs
critically
involved
shaping
structure
function
microenvironment
with
numerous
functions
regulating
behaviours,
such
as
metastasis,
invasion,
epithelial-mesenchymal
transition
(EMT).
can
interact
extensively
cells
by
producing
extracellular
vesicles
(EVs),
multiple
secreted
factors,
metabolites.
Notably,
CAF-derived
EVs
been
critical
mediators
therapy
resistance,
constitute
novel
targets
biomarkers
management.
This
review
aimed
to
summarize
biological
detailed
molecular
mechanisms
mediating
resistance
chemotherapy,
targeted
agents,
radiotherapy,
immunotherapy.
We
also
discussed
therapeutic
potential
clinical
management,
thereby
providing
strategy
for
enhancing
efficacy
improving
Biomolecules,
Год журнала:
2025,
Номер
15(2), С. 240 - 240
Опубликована: Фев. 7, 2025
Cancer
management
has
traditionally
depended
on
chemotherapy
as
the
mainstay
of
treatment;
however,
recent
advancements
in
targeted
therapies
and
immunotherapies
have
offered
new
options.
Ubiquitin-specific
proteases
(USPs)
emerged
promising
therapeutic
targets
cancer
treatment
due
to
their
crucial
roles
regulating
protein
homeostasis
various
essential
cellular
processes.
This
review
covers
following:
(1)
structural
functional
characteristics
USPs,
highlighting
involvement
key
cancer-related
pathways,
(2)
discovery,
chemical
structures,
mechanisms
action,
potential
clinical
implications
USP
inhibitors
therapy.
Particular
attention
is
given
role
enhancing
immunotherapy,
e.g.,
modulation
tumor
microenvironment,
effect
regulatory
T
cell
function,
influence
immune
checkpoint
pathways.
Furthermore,
this
summarizes
current
progress
challenges
trials
involving
We
also
discuss
complexities
achieving
target
selectivity,
ongoing
efforts
develop
more
specific
potent
inhibitors,
overcome
drug
resistance
synergize
with
existing
treatments.
finally
provide
a
perspective
future
directions
targeting
including
for
personalized
medicine
based
gene
mutations,
underscoring
significant
treatment.
By
elucidating
progress,
applications,
we
hope
that
could
serve
useful
resource
both
basic
scientists
clinicians
field
therapeutics.
World Journal of Surgical Oncology,
Год журнала:
2025,
Номер
23(1)
Опубликована: Фев. 20, 2025
Breast
cancer
is
a
prevalent
malignancy
worldwide,
and
its
treatment
has
increasingly
shifted
towards
precision
medicine,
with
immunotherapy
emerging
as
key
therapeutic
strategy.
Deubiquitination,
an
essential
epigenetic
modification,
regulated
by
deubiquitinating
enzymes
(DUBs)
plays
critical
role
in
immune
function
tumor
progression.
Ubiquitin-specific
proteases
(USPs),
prominent
subgroup
of
DUBs,
are
involved
regulating
cell
functions,
antigen
processing,
T
development
the
context
breast
cancer.
Certain
USPs
also
modulate
differentiation
cells,
such
myeloid-derived
suppressor
cells
(MDSCs)
regulatory
(Tregs),
within
microenvironment.
Furthermore,
several
influence
expression
PD-L1,
thus
affecting
efficacy
checkpoint
inhibitors.
The
overexpression
may
promote
evasion,
contributing
to
resistance.
This
review
elucidates
modulating
microenvironment
responses
Additionally,
it
discusses
effective
strategies
for
combining
USP
inhibitors
other
agents
enhance
outcomes.
Therefore,
targeting
presents
potential
overcome
drug
resistance,
offering
more
strategy
patients.
Cell Communication and Signaling,
Год журнала:
2025,
Номер
23(1)
Опубликована: Март 18, 2025
Protein
quality
control
(PQC)
plays
a
vital
role
in
maintaining
normal
heart
function,
as
cardiomyocytes
are
relatively
sensitive
to
misfolded
or
damaged
proteins,
which
tend
accumulate
under
pathological
conditions.
Ubiquitin-specific
protease
(USP)
is
the
largest
deubiquitinating
enzyme
family
and
key
component
of
ubiquitin
proteasome
system
(UPS),
non-lysosomal
protein
degradation
machinery
mediate
PQC
cells.
USPs
regulate
stability
activity
target
proteins
that
involve
intracellular
signaling,
transcriptional
inflammation,
antioxidation,
cell
growth.
Recent
studies
demonstrate
can
fibrosis,
lipid
metabolism,
glucose
homeostasis,
hypertrophic
response,
post-ischemic
recovery
death
such
apoptosis
ferroptosis
cardiomyocytes.
Since
myocardial
loss
an
important
cardiomyopathy,
therefore,
these
findings
suggest
UPSs
play
emerging
roles
cardiomyopathy.
This
review
briefly
summarizes
recent
literature
on
regulatory
occurrence
development
giving
us
new
insights
into
molecular
mechanisms
different
cardiomyopathy
potential
preventive
strategies
for
Persisting
programmed
cell
death-1
(PD-1)
signaling
impairs
T
effector
function,
which
is
highly
associated
with
exhaustion
and
immunotherapy
failure.
However,
the
mechanism
responsible
for
PD-1
deubiquitination
dysfunction
remains
unclear.
Here,
we
show
that
ubiquitin-specific
peptidase
24
(USP24)
promotes
protein
stability
by
removing
K48-linked
polyubiquitin.
Increased
interleukin-6
level
transcriptionally
activates
USP24
expression,
leads
to
stabilization.
Furthermore,
deficiency
reduces
levels
in
CD8
+
cells
attenuates
Egfr
L858R
-driven
lung
tumorigenesis
Usp24
C1695A
catalytic
deficient
mice.
Targeting
USP24-specific
inhibitor
USP24-i-101
boosts
cytotoxic
activity,
restrains
tumor
growth,
achieves
superior
therapeutic
effects
when
combined
anti-CTLA4
immunotherapy.
Clinically,
patients
cancer
exhibiting
high
expression
tumor-infiltrating
display
exhausted
features
unfavorable
responses
Our
findings
dissect
regulating
enhanced
reveal
as
a
potential
target
of
antitumor
