Journal of Neuro-Oncology,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 5, 2024
Abstract
Background
H3
histone
27
lysine
(H3K27)
trimethylation
(H3K27me3),
which
is
catalyzed
by
enhancer
of
zeste
homolog
2
(EZH2),
regulates
gene
expression
through
epigenetic
mechanisms.
H3K27me3
used
as
a
diagnostic
marker
for
diffuse
midline
glioma
and
surrogate
to
distinguish
posterior
fossa
ependymoma
A
B.
However,
the
clinical
significance
EZH2–H3K27me3
axis
in
astrocytoma,
IDH-mutant
has
not
been
reported,
prompting
this
investigation.
Methods
Thirty-three
patients
with
treated
at
our
institute
were
included
study.
Immunohistochemistry
(IHC)
targeting
H3K27me3,
H3K27M,
EZH2,
EZH
inhibitory
protein,
IDH1-R132H,
p53,
ATRX,
Ki-67,
MTAP
was
performed.
Kaplan–Meier
analysis
Cox
regression
performed
analyze
correlations
overall
survival
(OS)
progression-free
(PFS)
various
factors,
including
age,
World
Health
Organization
(WHO)
grade,
extent
resection,
immunohistochemical
results.
Results
The
mean
patient
age
40.6
±
11.0
years.
IHC
positive
19
negative
14
patients.
WHO
grade
Ki-67
index
significantly
higher
H3K27me3-positive
group
(
p
=
0.004
0.024,
respectively).
OS
PFS
shorter
0.002
0.026,
Furthermore,
EZH2
double-positive
associated
0.001
In
2/3,
double
positivity
linked
0.0053
0.0048,
Conclusion
Positivity
especially
could
be
poor
prognostic
factor
IDH-mutant.
These
results
suggest
utility
candidate
markers
estimating
malignancy
npj Precision Oncology,
Journal Year:
2025,
Volume and Issue:
9(1)
Published: Feb. 21, 2025
Abstract
Enhancer
of
zeste
homolog
2
(EZH2)
is
an
essential
epigenetic
regulator
H3K27
histone
methylation
and
mutated
or
overexpressed
in
a
wide
variety
cancers.
In
melanoma,
EZH2
overexpression
contributes
to
excessive
trimethylation
on
tumor
suppressor
genes
has
been
proposed
be
mechanism
progression
metastasis.
EZH2-targeted
therapies
have
successfully
used
treat
patients
with
follicular
lymphoma
epithelioid
sarcoma,
but
their
clinical
use
melanoma
not
described.
Here,
we
describe
pediatric
patient
multiply
relapsed
harboring
A692V
missense
mutation,
treated
adjuvantly
the
inhibitor
tazemetostat,
who
experienced
prolonged
relapse-free
survival.
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: April 12, 2024
Epigenetic
changes
are
heritable
in
gene
expression
without
the
nucleotide
sequence
of
genes.
play
an
important
role
development
cancer
and
process
malignancy
metastasis.
Previous
studies
have
shown
that
abnormal
epigenetic
can
be
used
as
biomarkers
for
disease
status
prediction.
The
reversibility
controllability
modification
also
provide
new
strategies
early
prevention
treatment.
In
addition,
corresponding
drug
has
reached
clinical
stage.
this
paper,
we
will
discuss
recent
progress
application
tumor
from
three
perspectives:
DNA
methylation,
non-coding
RNA,
histone
modification,
order
to
opportunities
additional
research
applications.
Life Metabolism,
Journal Year:
2024,
Volume and Issue:
3(4)
Published: May 6, 2024
Abstract
Histone
methylation
plays
a
crucial
role
in
tumorigenesis.
Enhancer
of
zeste
homolog
2
(EZH2)
is
histone
methyltransferase
that
regulates
chromatin
structure
and
gene
expression.
EZH2
inhibitors
(EZH2is)
have
been
shown
to
be
effective
treating
hematologic
malignancies,
while
their
effectiveness
solid
tumors
remains
limited.
One
the
major
challenges
treatment
hypoxic
tumor
microenvironment.
Hypoxia-inducible
factor
1-alpha
(HIF-1α)
key
hypoxia
responder
interacts
with
promote
progression.
Here
we
discuss
implications
relationship
between
for
expanding
application
EZH2is
tumors.
Journal of Translational Internal Medicine,
Journal Year:
2025,
Volume and Issue:
13(2), P. 156 - 169
Published: April 1, 2025
Aberrant
upregulation
or
mutations
of
EZH2
frequently
occur
in
human
cancers.
However,
the
clinical
benefits
inhibitors
(EZH2i)
remain
unsatisfactory
for
majority
solid
tumors.
Therefore,
there
is
an
urgent
need
to
develop
new
strategies
expand
therapeutic
EZH2i.
Nanocarriers
have
gained
increased
attention
due
their
advantages
prolonged
blood
circulation,
enhanced
cellular
uptake,
and
active
targeting
capabilities.
This
study
aims
address
challenges
EZH2i
GSK126's
limited
efficacy
severe
adverse
effects
against
A
nano
delivery
system
was
developed
by
encapsulating
GSK126
within
albumin
nanoparticles
(GSK126
NPs).
The
prepared
NPs
exhibited
a
small
spherical
core
with
average
diameter
30.09
nm
±
1.55
nm,
high
drug
loading
capacity
(16.59%
2.86%)
good
entrapment
efficiency
(99.53%
0.208%).
decreased
tumor
weight
volume
B16F10
xenograft
mice,
while
such
were
not
observed
free
group.
Subsequently,
histological
analysis
demonstrated
that
significantly
alleviated
lipid-associated
liver
toxicity.
Additionally,
can
partially
counteract
on
MDSCs,
particularly
decreasing
infiltration
M-MDSCs
into
Albumin-based
potent
anti-cancer
tolerable
effects,
providing
promising
opportunity
future
translation
treating
Cell Death and Disease,
Journal Year:
2024,
Volume and Issue:
15(7)
Published: July 23, 2024
Abstract
Invasion
and
migration
are
the
key
hallmarks
of
cancer,
aggressive
growth
is
a
major
factor
contributing
to
treatment
failure
poor
prognosis
in
glioblastoma.
Protein
arginine
methyltransferase
6
(PRMT6),
as
an
epigenetic
regulator,
has
been
confirmed
promote
malignant
proliferation
glioblastoma
cells
previous
studies.
However,
effects
PRMT6
on
cell
invasion
its
underlying
mechanisms
remain
elusive.
Here,
we
report
that
functions
driver
element
for
tumor
Bioinformatics
analysis
glioma
sample
detection
results
demonstrated
highly
expressed
mesenchymal
subtype
or
invasive
gliomas,
significantly
negatively
correlated
with
their
prognosis.
Inhibition
(using
shRNA
inhibitor
EPZ020411)
reduces
vitro,
whereas
overexpression
produces
opposite
effects.
Then,
identified
maintains
protein
stability
EZH2
by
inhibiting
degradation
protein,
thereby
mediating
cells.
Further
mechanistic
investigations
found
inhibits
transcription
TRAF6
activating
histone
methylation
mark
(H3R2me2a),
reducing
interaction
between
enhance
Xenograft
assay
HE
staining
showed
expression
could
vivo,
immunohistochemical
mouse
brain
tissue
sections
also
regulatory
relationship
PRMT6,
TRAF6,
EZH2.
Our
findings
illustrate
suppresses
via
H3R2me2a
facilitate
migration.
Blocking
PRMT6-TRAF6-EZH2
axis
promising
strategy
