Integrating multi-omics and experimental techniques to decode ubiquitinated protein modifications in hepatocellular carcinoma
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 11, 2025
Background
Ubiquitination,
a
critical
post-translational
modification,
plays
pivotal
role
in
regulating
protein
stability
and
activity,
influencing
various
aspects
of
cancer
development,
including
metabolic
reprogramming,
immune
evasion,
tumor
progression.
However,
the
specific
ubiquitination
hepatocellular
carcinoma
(HCC),
particularly
relation
to
microenvironment
(TME),
remains
poorly
understood.
This
study
aims
systematically
explore
shaping
TME
HCC,
with
focus
on
its
impact
progression
modulation.
Methods
We
performed
bioinformatics
analysis
by
integrating
multiple
publicly
available
HCC
datasets
assess
status
across
cell
types
TME,
plasma
cells,
fibroblasts,
endothelial
epithelial-mesenchymal
transition
(EMT)
cells.
Ubiquitination
scores
were
calculated
categorize
these
types,
survival
data,
along
spatial
transcriptomics,
employed
evaluate
how
different
levels
influence
In
vitro
experiments,
such
as
transwell,
CCK8,
wound
healing
assays,
used
further
investigate
key
gene
UBE2C
phenotypes.
Results
Our
revealed
that
ubiquitination-related
genes
are
significantly
upregulated
tissues,
high
expression
correlating
poor
prognosis
patients.
Pathway
showed
enriched
processes
cycle
regulation,
DNA
repair,
p53
signaling.
These
pathways
contribute
promoting
proliferation,
facilitating
matrix
remodeling,
enhancing
angiogenesis.
Notably,
UBE2C,
enzyme,
appears
play
potentially
inhibiting
anti-tumor
responses
reducing
system’s
ability
recognize
eliminate
Furthermore,
experimental
data
confirmed
overexpression
promotes
invasion,
metastasis,
supporting
remodeling.
Conclusion
reveals
multifaceted
regulatory
roles
HCC.
not
only
supports
proliferation
anti-apoptotic
functions
within
cells
but
also
modulating
activity
stromal
Among
all
genes,
emerges
potential
prognostic
biomarker
therapeutic
target
offering
new
directions
for
precision
treatment
future.
Язык: Английский
Antitumor Research Based on Drug Delivery Carriers: Reversing the Polarization of Tumor-Associated Macrophages
Molecular Pharmaceutics,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 27, 2025
The
development
of
malignant
tumors
is
a
complex
process
that
involves
the
tumor
microenvironment
(TME).
An
immunosuppressive
TME
presents
significant
challenges
to
current
cancer
therapies,
serving
as
key
mechanism
through
which
cells
evade
immune
detection
and
play
crucial
role
in
progression
metastasis.
This
impedes
optimal
effectiveness
immunotherapeutic
approaches,
including
cytokines,
checkpoint
inhibitors,
vaccines.
Tumor-associated
macrophages
(TAMs),
major
component
tumor-infiltrating
cells,
exhibit
dual
functionalities:
M1-like
TAMs
suppress
tumorigenesis,
while
M2-like
promote
growth
Consequently,
various
nanocarriers
aimed
at
polarizing
phenotypes
distinct
mechanisms
has
emerged
promising
therapeutic
strategy
inhibit
escape
enhance
antitumor
responses.
Review
covers
origin
types
TAMs,
common
pathways
regulating
macrophage
polarization,
progression,
strategies
targeting
aiming
provide
comprehensive
understanding
guidance
for
future
research
clinical
applications.
Язык: Английский
Exploring novel biomarkers and immunotherapeutic targets for biofeedback therapies to reveal the tumor-associated immune microenvironment through a multimetric analysis of kidney renal clear cell carcinoma
Discover Oncology,
Год журнала:
2025,
Номер
16(1)
Опубликована: Март 13, 2025
Kidney
renal
clear
cell
carcinoma
(KIRC)
constitutes
the
primary
subtype
of
carcinoma,
representing
75%
to
80%
cases
and
carrying
a
substantial
cancer-specific
mortality
rate
up
24%.
Despite
advancements
in
treatment
options,
KIRC
displays
notable
resistance
conventional
therapies,
emphasizing
need
for
innovative
targeted
immunotherapeutic
strategies.
Chromatin
regulators
(CRs),
pivotal
proteins
controlling
gene
expression
critical
biological
processes,
play
crucial
role
initiation
progression
KIRC.
This
study
employed
multi-omics
approach
evaluate
impact
CR-associated
genes
on
prognosis.
The
utilized
TCGA-KIRC
dataset
LASSO
Cox
regression
construct
validate
prognostic
model
that
focuses
influencing
research
investigated
interactions
among
characteristics,
clinical
parameters,
tumor
microenvironment,
immunotherapy,
drug
responsiveness.
Experimental
validation,
encompassing
various
techniques
such
as
culture,
transient
transfection,
qPCR,
Transwell
assays,
confirmed
robust
predictive
capability
BRD9
gene.
analysis
identified
risk
score
CRs
an
independent
factor
determining
Furthermore,
introduced
Nomogram
integrates
attributes
assessment.
Significantly,
exhibited
substantially
elevated
within
cells,
underscoring
its
driving
cancer
proliferation,
invasion,
migration.
These
findings
suggest
potential
tailored
immunotherapy
targeting
presents
framework
based
approaches,
seamlessly
incorporating
CRs.
holds
promise
improving
accuracy
prognosis
prediction
patients,
laying
foundation
development
immunotherapies.
Язык: Английский
Design and in silico analysis of a novel peptide-based multiepitope vaccine against glioblastoma multiforme by targeting tumor-associated macrophage
Heliyon,
Год журнала:
2024,
Номер
10(24), С. e40774 - e40774
Опубликована: Ноя. 28, 2024
Язык: Английский
Exploring the role of Disulfidptosis in glioma progression: insights into tumor heterogeneity and therapeutic potential through single-cell RNA sequencing
Discover Oncology,
Год журнала:
2024,
Номер
15(1)
Опубликована: Дек. 23, 2024
Gliomas,
particularly
glioblastoma
(GBM),
are
the
most
common
and
aggressive
primary
brain
tumors
in
adults,
characterized
by
high
malignancy
frequent
recurrence.
Despite
standard
treatments,
including
surgery,
radiotherapy,
chemotherapy,
prognosis
for
GBM
remains
poor,
with
a
median
survival
of
less
than
15
months
five-year
rate
below
10%.
Tumor
heterogeneity
resistance
to
treatment
create
significant
challenges
controlling
glioma
progression.
Therefore,
there
is
an
urgent
need
new
therapeutic
targets
strategies.
This
study
investigates
role
Disulfidptosis,
recently
discovered
form
programmed
cell
death,
gliomas.
Unlike
apoptosis
necrosis,
Disulfidptosis
driven
abnormal
accumulation
intracellular
disulfide
bonds,
leading
protein
misfolding
cytoskeletal
collapse,
cancer
cells
metabolic
dysregulation.
We
aim
explore
how
respond
identify
potential
analyzing
gliomas
at
single-cell
level
using
RNA
sequencing
(scRNA-seq).
scRNA-seq
data
from
patients
were
analyzed
uncover
differences
ferroptosis-related
pathways,
iron
metabolism
lipid
peroxidation.
Cellular
subpopulations
within
profiled
assess
their
sensitivity
underlying
mechanisms.
Survival
analysis
was
conducted
evaluate
clinical
relevance
Disulfidptosis-related
gene
expression.
Multiple
exhibit
varying
sensitivities
influenced
properties.
Dysregulated
antioxidant
mechanisms
identified
as
key
factors
impacting
sensitivity.
Glioma
microenvironment
signaling
pathways
also
play
regulating
Disulfidptosis.
These
findings
suggest
that
activating
may
provide
novel
strategies
overcome
offers
insights
into
progression
highlights
its
target.
By
leveraging
data,
research
uncovers
tumor
identifies
specific
populations
resistant
pave
way
personalized
improve
outcomes
patients.
Язык: Английский