Journal of Hematology & Oncology,
Journal Year:
2022,
Volume and Issue:
15(1)
Published: July 6, 2022
Abstract
The
tumor
microenvironment
(TME),
which
is
regulated
by
intrinsic
oncogenic
mechanisms
and
epigenetic
modifications,
has
become
a
research
hotspot
in
recent
years.
Characteristic
features
of
TME
include
hypoxia,
metabolic
dysregulation,
immunosuppression.
One
the
most
common
RNA
N6-methyladenosine
(m
6
A)
methylation,
widely
involved
regulation
physiological
pathological
processes,
including
development.
Compelling
evidence
indicates
that
m
A
methylation
regulates
transcription
protein
expression
through
shearing,
export,
translation,
processing,
thereby
participating
dynamic
evolution
TME.
Specifically,
methylation-mediated
adaptation
to
phenotypic
shift
immune
cells
synergistically
promote
formation
an
immunosuppressive
supports
proliferation
metastasis.
In
this
review,
we
have
focused
on
involvement
tumor-adaptive
described
detailed
linking
change
cell
biological
functions.
view
collective
data,
advocate
treating
as
complete
ecosystem
components
crosstalk
with
each
other
achieve
adaptive
changes.
Finally,
describe
potential
utility
methylation-targeted
therapies
immunotherapy
clinical
applications
challenges
faced,
aim
advancing
research.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(24)
Published: April 12, 2024
METTL3,
a
primary
methyltransferase
catalyzing
the
RNA
N6-methyladenosine
(m6A)
modification,
has
been
identified
as
an
oncogene
in
several
cancer
types
and
thus
nominated
potentially
effective
target
for
therapeutic
inhibition.
However,
current
options
using
this
strategy
are
limited.
In
study,
we
targeted
protein-protein
interactions
at
METTL3-METTL14
binding
interface
to
inhibit
complex
formation
subsequent
catalysis
of
m6A
modification.
Among
candidate
peptides,
RM3
exhibited
highest
anti-cancer
potency,
inhibiting
METTL3
activity
while
also
facilitating
its
proteasomal
degradation.
We
then
designed
stapled
peptide
inhibitor
(RSM3)
with
enhanced
stability
α-helical
secondary
structure
required
interaction.
Functional
transcriptomic
analysis
vivo
indicated
that
RSM3
induced
upregulation
programmed
cell
death-related
genes
cancer-promoting
signals.
Furthermore,
tumor
growth
was
significantly
suppressed
apoptosis
upon
treatment,
accompanied
by
increased
degradation,
reduced
global
methylation
levels
two
models.
This
exploits
mechanism
distinct
from
other
small-molecule
competitive
inhibitors
oncogenic
activity.
Our
findings
collectively
highlight
potential
targeting
therapies
through
peptide-based
inhibition
proteolytic
Biomedicine & Pharmacotherapy,
Journal Year:
2020,
Volume and Issue:
131, P. 110731 - 110731
Published: Sept. 10, 2020
RNA
methylation
is
a
post-transcriptional
level
of
regulation.
At
present,
more
than
150
kinds
modifications
have
been
identified.
They
are
widely
distributed
in
messenger
(mRNA),
transfer
(tRNA),
ribosomal
(rRNA),
noncoding
small
(sncRNA)
and
long-chain
non-coding
(lncRNA).
In
recent
years,
with
the
discovery
related
proteins
development
high-throughput
sequencing
technology,
mystery
has
gradually
revealed,
its
biological
function
application
value
emerged.
this
review,
large
number
research
results
years
collected.
Through
systematic
summary
refinement,
review
introduced
modification-related
technologies,
as
well
functions
methylation,
expressions
applications
methylation-related
genes
physiological
or
pathological
states
such
cancer,
immunity
virus
infection,
discussed
potential
therapeutic
strategies.
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2021,
Volume and Issue:
40(1)
Published: Aug. 24, 2021
Abstract
Background
Autophagy
is
an
intracellular
degradation
system
that
removes
unnecessary
or
dysfunctional
components
and
recycles
them
for
other
cellular
functions.
Over
the
years,
a
mutual
regulation
between
lipid
metabolism
autophagy
has
been
uncovered.
Methods
This
narrative
review
discussing
connection
SCD1
autophagic
process,
along
with
modality
through
which
this
crosstalk
can
be
exploited
therapeutic
purposes.
Results
Fatty
acids,
depending
on
species,
have
either
activating
inhibitory
roles
autophagy.
In
turn,
regulates
mobilization
of
fat
from
deposits,
such
as
droplets,
lipids
to
prevent
lipotoxicity
.
describes
by
in
cancer
cells,
focusing
role
stearoyl-CoA
desaturase
1
(SCD1),
key
enzyme
involved
synthesis
monounsaturated
fatty
acids.
plays
important
cancer,
promoting
cell
proliferation
metastasis.
The
more
complex
since
it
act
protecting
against
onset
tumor
growth.
Mounting
evidence
indicates
are
tightly
interconnected.
Conclusion
Here,
we
discuss
controversial
findings
inducer
inhibitor
highlighting
how
these
activities
may
result
promotion
inhibition
upon
degree
heterogeneity
plasticity.
Cancer Research,
Journal Year:
2021,
Volume and Issue:
81(11), P. 2847 - 2860
Published: April 1, 2021
Abstract
The
roles
of
RNA
modification
during
organ
metastasis
cancer
cells
are
not
known.
Here
we
established
breast
lung
by
three
rounds
selection
metastatic
subpopulations
in
vivo
and
designated
them
as
BCLMF3
cells.
In
these
cells,
mRNA
N6-methyladenosine
(m6A)
methyltransferase
METTL3
were
increased,
while
the
demethylase
FTO
was
decreased.
Epi-transcriptome
transcriptome
analyses
together
with
functional
studies
identified
keratin
7
(KRT7)
a
key
effector
for
m6A-induced
metastasis.
Specifically,
increased
methylated
KRT7-AS
at
A877
to
increase
stability
KRT7-AS/KRT7
duplex
via
IGF2BP1/HuR
complexes.
Furthermore,
YTHDF1/eEF-1
involved
FTO-regulated
translational
elongation
KRT7
mRNA,
A950
exon
6
site
methylation.
clinical
confirmed
essential
KRT7,
KRT7-AS,
progression
cancer.
Collectively,
m6A
promotes
increasing
translation
KRT7.
Significance:
This
study
suggests
that
is
driver
potential
therapeutic
target
Cell Death and Disease,
Journal Year:
2021,
Volume and Issue:
12(6)
Published: June 9, 2021
Abstract
Recently,
the
regulatory
role
of
epigenetic
modifications
in
occurrence
and
development
malignant
tumors
has
attracted
extensive
attention.
RNA
m6A
methylation
is
most
abundant
modification
eukaryotic
cells
regulates
transcription,
processing,
splicing,
degradation,
translation.
As
important
biomarkers,
miRNAs
play
a
crucial
diagnosis
treatment
diseases
as
well
anti-tumor
drugs.
increasing
evidence
shown
that
plays
vital
regulating
miRNA
biosynthesis.
We,
herein,
have
reviewed
enzyme
system
involved
crosstalk
between
cancer.
In
addition,
we
discussed
potential
clinical
applications
possible
directions
this
field
future.
Biomedicine & Pharmacotherapy,
Journal Year:
2020,
Volume and Issue:
127, P. 110098 - 110098
Published: April 13, 2020
N6-methyladenosine
(m6A)
is
the
most
abundant
RNA
modification;
m6A
modifications
are
installed
by
methyltransferases,
removed
demethylases
and
recognized
reader
proteins.
M6A
plays
crucial
roles
in
a
variety
of
biological
processes
regulating
target
translation,
splicing,
nuclear
export,
decay.
Since
establishment
methylated
immunoprecipitation-sequencing
methodology,
over
three
hundred
articles
about
modulators,
including
"writers",
"erasers"
"readers",
have
been
reported
last
four
years.
In
addition,
an
increasing
number
molecular
mechanisms
underlying
methylation
human
cancers
comprehensively
clarified.
The
recently
emerged
modulators
cancer
cell
proliferation,
cycle
progression,
migration
invasion,
apoptosis,
autophagy
remain
to
be
summarized.
Hence,
this
review
specifically
summarizes
these
recent
advances
understanding
tumorigenesis
progression.
we
discuss
prospect
using
modulator
as
new
diagnostic
biomarker
therapeutic
for
cancers.
Theranostics,
Journal Year:
2021,
Volume and Issue:
11(9), P. 4549 - 4566
Published: Jan. 1, 2021
Epigenetic
regulation
involves
a
range
of
sophisticated
processes
which
contribute
to
heritable
alterations
in
gene
expression
without
altering
DNA
sequence.
Regulatory
events
predominantly
include
methylation,
chromatin
remodeling,
histone
modifications,
non-coding
RNAs
(ncRNAs),
and
RNA
modification.
As
the
most
prevalent
modification
eukaryotic
cells,
N6-methyladenosine
(m6A)
methylation
actively
participates
modulation
metabolism.
Notably,
accumulating
evidence
has
revealed
complicated
interrelations
occurring
between
m6A
other
well-known
epigenetic
modifications.
Their
crosstalk
conspicuously
triggers
further
yielding
profound
impacts
on
variety
physiological
pathological
processes,
especially
tumorigenesis.
Herein,
we
provide
an
up-to-date
review
this
emerging
hot
area
biological
research,
summarizing
interplay
regulators,
highlighting
their
underlying
functions
reprogramming.
