Molecular Medicine,
Journal Year:
2024,
Volume and Issue:
30(1)
Published: June 17, 2024
Abstract
Glioma
is
the
most
common
malignant
tumor
of
central
nervous
system,
with
EZH2
playing
a
crucial
regulatory
role.
This
study
further
explores
abnormal
expression
and
its
mechanisms
in
regulating
glioma
progression.
Additionally,
it
was
found
that
IHMT-337
can
potentially
be
therapeutic
agent
for
glioma.
The
prognosis,
expression,
localization
were
determined
using
bioinformatics,
IHC
staining,
Western
blot
(WB)
analysis,
immunofluorescence
(IF)
localization.
effects
on
cell
function
assessed
CCK-8
assays,
Transwell
wound
healing
assays.
Public
databases
RT-qPCR
utilized
to
identify
downstream
targets.
these
targets
elucidated
MS-PCR
WB
analysis.
efficacy
demonstrated
through
IC50
measurements,
RT-qPCR.
cells
vitro
evaluated
EdU
incorporation
flow
cytometry.
potential
as
treatment
blood–brain
barrier
(BBB)
model
an
orthotopic
model.
Our
research
confirms
significantly
elevated
gliomas,
correlating
patient
prognosis.
facilitates
proliferation,
migration,
invasion
alongside
promoting
SLC12A5
DNA
methylation.
By
activates
WNK1-OSR1-NKCC1
pathway,
enhancing
interaction
ERM
promote
migration.
inhibit
WNK1
activation,
thereby
suppressing
inhibits
proliferation
arrests
cycle.
has
cross
BBB
successfully
inhibited
progression
vivo.
expands
our
understanding
EZH2-
axis
laying
new
foundation
clinical
translation
offering
insights
precision
therapy.
JNCI Journal of the National Cancer Institute,
Journal Year:
2023,
Volume and Issue:
115(11), P. 1355 - 1363
Published: May 25, 2023
Abstract
Background
National
Cancer
Institute-Children’s
Oncology
Group
Pediatric
Molecular
Analysis
for
Therapy
Choice
assigns
patients
aged
1-21
years
with
refractory
solid
tumors,
brain
lymphomas,
and
histiocytic
disorders
to
phase
II
trials
of
molecularly
targeted
therapies
based
on
detection
predefined
genetic
alterations.
Patients
whose
tumors
harbored
EZH2
mutations
or
loss
SMARCB1
SMARCA4
by
immunohistochemistry
were
treated
inhibitor
tazemetostat.
Methods
received
tazemetostat
28-day
cycles
until
disease
progression
intolerable
toxicity
(max
26
cycles).
The
primary
endpoint
was
objective
response
rate;
secondary
endpoints
included
progression-free
survival
tolerability
Results
Twenty
(median
age
=
5
years)
enrolled,
all
evaluable
toxicities.
most
frequent
diagnoses
atypical
teratoid
rhabdoid
tumor
(n
8)
malignant
4).
Actionable
alterations
consisted
16),
mutation
3),
1).
One
observed
in
a
patient
non-Langerhans
cell
histiocytosis
(26
cycles,
1200
mg/m2/dose
twice
daily).
Four
had
best
stable
disease:
epithelioid
sarcoma
2),
1),
renal
medullary
carcinoma
Six-month
35%
(95%
confidence
interval
[CI]
15.7%
55.2%)
6-month
overall
45%
CI
23.1%
64.7%).
Treatment-related
adverse
events
consistent
prior
reports.
Conclusions
Although
did
not
meet
its
efficacy
this
population
pediatric
(objective
rate
5%,
90%
1%
20%),
25%
multiple
histologic
experienced
prolonged
6
months
over
(range
9-26
cycles),
suggesting
potential
effect
stabilization.
Journal of Clinical Investigation,
Journal Year:
2023,
Volume and Issue:
133(2)
Published: Jan. 16, 2023
Epigenetic
remodeling
is
a
molecular
hallmark
of
gliomas,
and
it
has
been
identified
as
key
mediator
glioma
progression.
dysregulation
contributes
to
gliomagenesis,
tumor
progression,
responses
immunotherapies,
well
determining
clinical
features.
This
epigenetic
includes
changes
in
histone
modifications,
chromatin
structure,
DNA
methylation,
all
which
are
driven
by
mutations
genes
such
3
(H3C1
H3F3A),
isocitrate
dehydrogenase
1/2
(IDH1/2),
α-thalassemia/mental
retardation,
X-linked
(ATRX),
additional
remodelers.
Although
much
the
initial
research
primarily
how
aberrations
impacted
progression
solely
examining
cells,
recent
studies
have
aimed
at
establishing
role
alterations
shaping
microenvironment
(TME).
In
this
review,
we
discuss
mechanisms
these
phenomena
remodel
TME
current
therapies
targeting
affect
immune
response
therapeutic
outcomes.
Understanding
link
between
provides
insights
into
implementation
epigenetic-targeting
improve
antitumor
response.
Cancers,
Journal Year:
2022,
Volume and Issue:
14(15), P. 3743 - 3743
Published: July 31, 2022
Glioblastoma
(GBM)
is
an
aggressive
tumor
of
the
central
nervous
system
categorized
by
World
Health
Organization
as
a
Grade
4
astrocytoma.
Despite
treatment
with
surgical
resection,
adjuvant
chemotherapy,
and
radiation
therapy,
outcomes
remain
poor,
median
survival
only
14-16
months.
Although
regression
often
observed
initially
after
treatment,
long-term
recurrence
or
progression
invariably
occurs.
Tumor
growth,
invasion,
mediated
unique
population
glioblastoma
stem
cells
(GSCs).
Their
high
mutation
rate
dysregulated
transcriptional
landscape
augment
their
resistance
to
conventional
chemotherapy
explaining
poor
in
patients.
Consequently,
GSCs
have
emerged
targets
interest
new
paradigms.
Here,
we
review
properties
GSCs,
including
interactions
hypoxic
microenvironment
that
drives
proliferation.
We
discuss
vital
signaling
pathways
mediate
stemness,
self-renewal,
proliferation,
Notch,
epidermal
growth
factor
receptor,
phosphatidylinositol
3-kinase/Akt,
sonic
hedgehog,
transforming
beta,
Wnt,
signal
transducer
activator
transcription
3,
inhibitors
differentiation
pathways.
also
epigenomic
changes
influence
state,
DNA
methylation,
histone
methylation
acetylation,
miRNA
expression.
The
constituent
molecular
components
regulators
represent
potential
sites
for
targeted
representative
examples
inhibitory
molecules
pharmaceuticals
are
discussed.
Continued
investigation
into
candidate
therapeutics
needed
discover
effective
treatments
GBM
improve
survival.
Oncogene,
Journal Year:
2023,
Volume and Issue:
42(14), P. 1088 - 1100
Published: Feb. 15, 2023
Abstract
PRMT6,
a
type
I
arginine
methyltransferase,
di-methylates
the
residues
of
both
histones
and
non-histones
asymmetrically.
Increasing
evidence
indicates
that
PRMT6
plays
tumor
mediator
involved
in
human
malignancies.
Here,
we
aim
to
uncover
essential
role
underlying
mechanisms
promoting
glioblastoma
(GBM)
proliferation.
Investigation
expression
glioma
tissues
demonstrated
is
overexpressed,
elevated
negatively
correlated
with
poor
prognosis
glioma/GBM
patients.
Silencing
inhibited
GBM
cell
proliferation
induced
cycle
arrest
at
G0/G1
phase,
while
overexpressing
had
opposite
results.
Further,
found
attenuates
protein
stability
CDKN1B
by
its
degradation.
Subsequent
mechanistic
investigations
showed
maintains
transcription
CDC20
activating
histone
methylation
mark
(H3R2me2a),
interacts
destabilizes
CDKN1B.
Rescue
experimental
results
confirmed
promotes
ubiquitinated
degradation
via
CDC20.
We
also
verified
inhibitor
(EPZ020411)
could
attenuate
proliferative
effect
cells.
Our
findings
illustrate
an
epigenetic
mediator,
H3R2me2a
mediate
facilitate
progression.
Targeting
PRMT6-CDC20-CDKN1B
axis
might
be
promising
therapeutic
strategy
for
GBM.
Genes & Development,
Journal Year:
2024,
Volume and Issue:
38(11-12), P. 473 - 503
Published: June 1, 2024
The
discovery
of
epigenetic
modulators
(writers,
erasers,
readers,
and
remodelers)
has
shed
light
on
previously
underappreciated
biological
mechanisms
that
promote
diseases.
With
these
insights,
novel
biomarkers
innovative
combination
therapies
can
be
used
to
address
challenging
difficult
treat
disease
states.
This
review
highlights
key
writers,
remodelers
control,
as
well
their
connection
with
states
recent
advances
in
associated
therapies.
Cancer Cell International,
Journal Year:
2023,
Volume and Issue:
23(1)
Published: Oct. 11, 2023
Abstract
Glioma
is
the
most
aggressive
and
malignant
type
of
primary
brain
tumor,
comprises
majority
central
nervous
system
deaths,
categorized
into
different
subgroups
according
to
its
histological
characteristics,
including
astrocytomas,
oligodendrogliomas,
glioblastoma
multiforme
(GBM),
mixed
tumors.
The
forkhead
box
(FOX)
transcription
factors
comprise
a
collection
proteins
that
play
various
roles
in
numerous
complex
molecular
cascades
have
been
discovered
be
differentially
expressed
distinct
glioma
subtypes.
FOXM1
FOXOs
recognized
as
crucial
tumor
cells,
cells.
Accumulating
data
indicates
acts
an
oncogene
types
cancers,
significant
part
studies
has
investigated
function
glioma.
Although
recent
considered
FOXO
suppressors,
there
are
pieces
evidence
they
may
oncogenic
role.
This
review
will
discuss
subtle
functions
gliomas,
dissecting
their
regulatory
network
with
other
proteins,
microRNAs
role
progression,
stem
cell
differentiation
therapy
resistance/sensitivity,
alongside
highlighting
pharmacological
progress
for
modulating
expression.
