GC-derived exosomal circMAN1A2 promotes cancer progression and suppresses T-cell antitumour immunity by inhibiting FBXW11-mediated SFPQ degradation
Journal of Experimental & Clinical Cancer Research,
Год журнала:
2025,
Номер
44(1)
Опубликована: Янв. 25, 2025
Abstract
Background
Exosomes,
as
extracellular
membrane
vesicles,
play
important
roles
in
intercellular
communication
and
can
influence
tumour
progression.
Circular
RNAs
(circRNAs)
have
been
reported
various
malignancies
are
also
components
of
exosomes.
However,
the
role
exosomal
circRNAs
gastric
cancer
(GC)
progression
has
not
completely
clarified.
Methods
The
enriched
GC
were
identified
using
circRNA
sequencing.
biological
function
circMAN1A2
was
investigated
a
series
vitro
vivo
experiments.
PKH-67
staining
used
to
label
molecular
mechanism
via
mass
spectrometry,
immunoprecipitation,
Western
blot,
single-cell
RNA-sequencing
data
analyses.
Results
In
our
study,
we
determined
that
(hsa_circ_0000118)
GC-derived
Higher
expression
related
poor
survival
patients
(HR
=
2.917,
p
0.0120).
Exosomal
promoted
suppressed
antitumour
activity
T
cells.
Moreover,
bound
SFPQ
cells
cells,
promoting
G1/S
phase
transition
cell
cycle
while
inhibiting
activation
receptor
signalling
pathway
decrease
activity.
Mechanistically,
competed
with
FBXW11
for
binding
SFPQ,
preventing
FBXW11-mediated
k48-linked
ubiquitination
protein
degradation,
thereby
stabilizing
expression.
Conclusions
Our
work
confirms
critical
immunosuppression
GC.
This
novel
axis
circMAN1A2-SFPQ
provides
new
insights
into
circRNA-based
diagnostic
therapeutic
strategies.
Язык: Английский
Exosomal circ‐0100519 promotes breast cancer progression via inducing M2 macrophage polarisation by USP7/NRF2 axis
Clinical and Translational Medicine,
Год журнала:
2024,
Номер
14(8)
Опубликована: Авг. 1, 2024
Abstract
Background
Breast
cancer
(BC)
is
one
of
the
most
prevalent
malignant
tumours
that
threatens
women
health
worldwide.
It
has
been
reported
circular
RNAs
(circRNAs)
play
an
important
role
in
regulating
tumour
progression
and
microenvironment
(TME)
remodelling.
Methods
Differentially
expression
characteristics
immune
correlations
circRNAs
BC
were
verified
using
high‐throughput
sequencing
bioinformatic
analysis.
Exosomes
characterised
by
nanoparticle
transmission
electron
microscopy
tracking
The
biological
function
circ‐0100519
development
was
demonstrated
both
vitro
vivo.
Western
blotting,
RNA
pull‐down,
immunoprecipitation,
flow
cytometry,
luciferase
reporter
conducted
to
investigate
underlying
mechanism.
Results
Circ‐0100519
significant
abundant
tissues
related
poor
prognosis.
can
be
encapsulated
into
secreted
exosomes,
thereby
promoting
cell
invasion
metastasis
via
inducing
M2‐like
macrophages
polarisation.Mechanistically,
acted
as
a
scaffold
enhance
interaction
between
deubiquitinating
enzyme
ubiquitin‐specific
protease
7
(USP7)
nuclear
factor‐like
2
(NRF2)
macrophages,
USP7‐mediated
deubiquitination
NRF2.
Additionally,
HIF‐1α
could
upstream
effector
transcription.
Conclusions
Our
study
revealed
exosomal
potential
biomarker
for
diagnosis
prognosis,
inhibitor
PX‐478
may
provide
therapeutic
target
BC.
Язык: Английский
Unravelling the role of ubiquitin-specific proteases in breast carcinoma: insights into tumour progression and immune microenvironment modulation
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.
Язык: Английский
Tumor-derived extracellular vesicles: key drivers of immunomodulation in breast cancer
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Март 4, 2025
Breast
cancer
(BC)
remains
a
significant
global
health
challenge
characterized
by
its
heterogeneity
and
treatment
complexities.
Extracellular
vesicles
(EVs)
are
small
membranous
particles
released
cells,
facilitating
intercellular
communication
transporting
bioactive
molecules
such
as
proteins,
lipids,
nucleic
acids.
Tumor-derived
EVs
have
emerged
pivotal
regulators
in
the
tumor
microenvironment
(TME)
drivers
of
BC
progression.
These
carry
diverse
cargoes
molecules,
influencing
critical
processes
immune
modulation,
angiogenesis,
metastasis.
By
altering
behaviors
cells
including
macrophages,
dendritic
T
tumor-derived
contribute
to
evasion
growth.
Furthermore,
play
role
mediating
drug
resistance,
impacting
effectiveness
therapeutic
interventions.
Understanding
multifaceted
roles
is
essential
for
development
innovative
strategies.
Targeting
pathways
mediated
holds
promise
enhancing
efficacy
treatments
improving
patient
outcomes.
This
comprehensive
review
provides
insights
into
intricate
interactions
modulation
progression,
highlighting
potential
targets
avenues
novel
therapies.
Язык: Английский
Exosomal circRNAs: key modulators in breast cancer progression
Cell Death Discovery,
Год журнала:
2025,
Номер
11(1)
Опубликована: Апрель 24, 2025
Abstract
Breast
cancer
(BC)
poses
significant
challenges
globally,
necessitating
a
deeper
understanding
of
its
complexities.
Exosomes
are
cell-specific
secreted
extracellular
vesicles
interest,
characterized
by
lipid
bilayer
structure.
can
carry
variety
bioactive
components,
including
nucleic
acids,
lipids,
amino
and
small
molecules,
to
mediate
intercellular
signaling.
CircRNAs
novel
class
single-stranded
RNA
closed-loop
mainly
exert
ceRNA
functions
intricately
modulate
gene
expression
signaling
pathways
in
breast
cancer,
influencing
tumor
progression
therapeutic
responses.
The
unique
packaging
circRNAs
within
exosomes
serves
as
genetic
information
transmitters,
facilitating
communication
between
BC
cells
microenvironmental
cells,
thereby
regulating
critical
aspects
progression,
immune
evasion,
drug
resistance.
Besides,
exosomal
possess
the
capabilities
serving
diagnostic
biomarkers
BC,
due
their
stability,
specificity,
regulatory
roles
tumorigenesis
metastasis.
Therefore,
this
review
aims
elucidate
mechanisms
well
potential
for
diagnosis
therapeutics.
ongoing
investigations
will
potentially
revolutionize
treatment
paradigms
improve
patient
outcomes
BC.
Язык: Английский