Frontiers in Cell and Developmental Biology,
Год журнала:
2022,
Номер
10
Опубликована: Сен. 13, 2022
Background:
Lung
adenocarcinoma
(LUAD)
is
the
most
common
type
of
lung
cancer
with
a
complex
tumor
microenvironment.
Neddylation,
as
post-translational
modification,
plays
vital
role
in
development
LUAD.
To
date,
no
study
has
explored
potential
neddylation-associated
genes
for
LUAD
classification,
prognosis
prediction,
and
treatment
response
evaluation.
Methods:
Seventy-six
prognostic
were
identified
by
Univariate
Cox
analysis.
Patients
classified
into
two
patterns
based
on
unsupervised
consensus
clustering
In
addition,
10-gene
signature
was
constructed
using
LASSO-Cox
multivariate
stepwise
regression
approach.
Results:
Substantial
differences
observed
between
terms
prognosis.
Compared
neddylation
cluster2,
cluster1
exhibited
low
levels
immune
infiltration
that
promote
progression.
Additionally,
neddylation-related
risk
score
correlated
clinical
parameters
it
can
be
good
predictor
patient
outcomes,
gene
mutation
levels,
chemotherapeutic
responses.
Conclusion:
Neddylation
distinguish
microenvironment
patients
Prognostic
signatures
predict
outcomes
guide
personalized
treatment.
Journal of Personalized Medicine,
Год журнала:
2023,
Номер
13(3), С. 379 - 379
Опубликована: Фев. 21, 2023
Objective:
To
study
the
role
of
MLN4924
in
corneal
stem
cell
maintenance
and
injury
repair.
Methods:
In
experiments,
Sprague–Dawley
(SD)
rat
epithelial
cells
were
co-cultured
with
mitomycin
C-inactivated
mouse
feeder
a
supplemental
hormonal
medium
(SHEM)
or
without
MLN4924.
Cells
photographed
using
an
optical
microscope.
Furthermore,
we
performed
crystal
violet,
polymerase
chain
reaction
(PCR),
immunofluorescence
staining
on
limbal
(LSCs).
animal
scraped
epithelium
central
diameter
4
mm
SD
rats.
The
area
defect
was
calculated
by
fluorescein
sodium
staining.
Results:
LSCs
group
had
significantly
proliferated.
treatment
evidently
enhanced
clone
formation
rate
LSCs.
expression
levels
Ki67,
p63,
ABCG2,
Bmi1,
C/EBPδ
increased
after
treatment,
whereas
K12
decreased.
At
12
24
h
scraping,
recovery
eyes
MLN4924-treated
rats
accelerated.
Conclusions:
can
maintain
stemness,
reduce
differentiation,
promote
proliferative
capacity
LSCs,
accelerate
wound
healing
Abstract
Immunosuppressive
cells
play
important
roles
in
generating
an
immunosuppressive
tumor
microenvironment
and
facilitating
immune
escape.
However,
the
molecular
mechanisms
underlying
their
effects
remain
unclear.
UBA3,
sole
catalytic
subunit
of
neural
precursor
cell
expressed
developmentally
down-regulated
protein
8
(NEDD8)-activating
enzyme
E1,
is
highly
various
human
malignancies,
along
with
activated
neddylation
pathway.
In
this
study,
we
investigated
relationships
between
UBA3-dependent
pathway
infiltration
several
populations
lung
adenocarcinoma
(LUAD).
We
explored
regulatory
UBA3
LUAD
by
using
mRNA
sequencing
functional
enrichment
analyses.
Correlations
infiltrates
were
assessed
Western
blotting,
real-time
PCR,
analyses
public
databases.
found
elevated
levels
expression
tissues
compared
to
adjacent
normal
tissues.
Blocking
promoted
accumulation
phosphorylated
nuclear
factor
kappa
light
polypeptide
gene
enhancer
B-cells
inhibitor
(p-IκBα),
inhibiting
cell-derived
cytokines
such
as
C–C
motif
chemokine
ligand
(CCL)
2,
C-X-C
(CXCL)1,
CXCL2,
colony-stimulating
(CSF)
1,
CSF2
interleukin
(IL)-6,
IL-1B.
Moreover,
overexpression
was
associated
secretion
these
cytokines,
recruitment
including
tumor-associated
macrophages
(TAMs),
plasmacytoid
dendritic
(pDCs),
Th2
T-regulatory
(Tregs).
This
could
facilitate
escape
malignant
progression
LUAD.
Our
findings
provide
new
insights
into
role
establishing
modulating
B
(NF-кB)
signaling
Cells,
Год журнала:
2023,
Номер
12(22), С. 2620 - 2620
Опубликована: Ноя. 13, 2023
Canonical
Wnt
signaling
is
essential
for
a
plethora
of
biological
processes
ranging
from
early
embryogenesis
to
aging.
Malfunctions
this
crucial
pathway
are
associated
with
various
developmental
defects
and
diseases,
including
cancer.
Although
TCF/LEF
transcription
factors
(TCF/LEFs)
known
be
pathway,
the
regulation
their
intracellular
levels
not
completely
understood.
Here,
we
show
that
lysine
demethylase
KDM2A
promotes
proteasomal
destabilization
TCF/LEFs
independently
its
domain.
We
found
KDM2A-mediated
dependent
on
zinc
finger
CXXC
Furthermore,
identified
C-terminal
region
TCF7L2
domain
as
domains
responsible
interaction
between
two
proteins.
Our
study
also
first
endogenous
proteins
undergo
degradation
in
neddylation-dependent
manner.
reveal
new
mechanism
affects
canonical
by
regulating
through
KDM2A-promoted
degradation.
Frontiers in Cell and Developmental Biology,
Год журнала:
2022,
Номер
10
Опубликована: Сен. 13, 2022
Background:
Lung
adenocarcinoma
(LUAD)
is
the
most
common
type
of
lung
cancer
with
a
complex
tumor
microenvironment.
Neddylation,
as
post-translational
modification,
plays
vital
role
in
development
LUAD.
To
date,
no
study
has
explored
potential
neddylation-associated
genes
for
LUAD
classification,
prognosis
prediction,
and
treatment
response
evaluation.
Methods:
Seventy-six
prognostic
were
identified
by
Univariate
Cox
analysis.
Patients
classified
into
two
patterns
based
on
unsupervised
consensus
clustering
In
addition,
10-gene
signature
was
constructed
using
LASSO-Cox
multivariate
stepwise
regression
approach.
Results:
Substantial
differences
observed
between
terms
prognosis.
Compared
neddylation
cluster2,
cluster1
exhibited
low
levels
immune
infiltration
that
promote
progression.
Additionally,
neddylation-related
risk
score
correlated
clinical
parameters
it
can
be
good
predictor
patient
outcomes,
gene
mutation
levels,
chemotherapeutic
responses.
Conclusion:
Neddylation
distinguish
microenvironment
patients
Prognostic
signatures
predict
outcomes
guide
personalized
treatment.