Frontiers in Oncology,
Год журнала:
2024,
Номер
14
Опубликована: Ноя. 29, 2024
Gastric
cancer
(GC)
is
one
of
the
leading
causes
cancer-related
death
worldwide.
N6-methyladenosine
(m6A)
modification
most
prominent
epigenetic
eukaryotic
mRNAs,
and
methyltransferase-like
3
(METTL3),
a
core
component
methyltransferase
complex,
catalyzes
m6A
modification.
The
results
previous
studies
indicate
that
expression
level
METTL3
significantly
elevated
in
gastric
tissues
cells.
In
addition,
fluctuations
levels
induced
by
are
closely
associated
with
malignant
progression
tumors
as
well
poor
prognosis
patients
cancer.
this
review,
we
focus
on
potential
mechanism
cancer,
through
our
analysis,
suggest
targeting
could
be
new
therapeutic
tool
for
treating
GC.
Drug
resistance
in
cancer
cells
significantly
diminishes
treatment
efficacy,
leading
to
recurrence
and
metastasis.
A
critical
factor
contributing
this
is
the
epigenetic
alteration
of
gene
expression
via
RNA
modifications,
such
as
N6-methyladenosine
(m6A),
N1-methyladenosine
(m1A),
5-methylcytosine
(m5C),
7-methylguanosine
(m7G),
pseudouridine
(Ψ),
adenosine-to-inosine
(A-to-I)
editing.
These
modifications
are
pivotal
regulating
splicing,
translation,
transport,
degradation,
stability.
Governed
by
"writers,"
"readers,"
"erasers,"
impact
numerous
biological
processes
progression,
including
cell
proliferation,
stemness,
autophagy,
invasion,
apoptosis.
Aberrant
can
lead
drug
adverse
outcomes
various
cancers.
Thus,
targeting
modification
regulators
offers
a
promising
strategy
for
overcoming
enhancing
efficacy.
This
review
consolidates
recent
research
on
role
prevalent
resistance,
with
focus
m6A,
m1A,
m5C,
m7G,
Ψ,
A-to-I
Additionally,
it
examines
regulatory
mechanisms
linked
underscores
existing
limitations
field.
Abstract
Translational
regulation
is
an
important
step
in
the
control
of
gene
expression.
In
cancer
cells,
orchestration
both
global
protein
synthesis
and
selective
translation
specific
mRNAs
promote
tumor
cell
survival,
angiogenesis,
transformation,
invasion
metastasis.
N6-methyladenosine
(m6A),
most
prevalent
mRNA
modification
higher
eukaryotes,
impacts
translation.
Over
past
decade,
development
m6A
mapping
tools
has
facilitated
comprehensive
functional
investigations,
revealing
involvement
this
chemical
mark,
together
with
its
writer
METTL3,
promoting
oncogenes
suppressor
transcripts,
impact
being
context-dependent.
This
review
aims
to
consolidate
our
current
understanding
how
METTL3
shape
realm
biology.
addition,
it
delves
into
role
cytoplasmic
synthesis,
operating
independently
catalytic
activity.
Ultimately,
goal
provide
critical
insights
interplay
between
m6A,
translational
cancer,
offering
a
deeper
comprehension
mechanisms
sustaining
tumorigenesis.
Abstract
RNA‐modifying
proteins,
classified
as
“writers,”
“erasers,”
and
“readers,”
dynamically
modulate
RNA
by
adding,
removing,
or
interpreting
chemical
groups,
thereby
influencing
stability,
functionality,
interactions.
To
date,
over
170
distinct
modifications
more
than
100
enzymes
have
been
identified,
with
ongoing
research
expanding
these
numbers.
Although
significant
progress
has
made
in
understanding
modification,
the
regulatory
mechanisms
that
govern
proteins
themselves
remain
insufficiently
explored.
Post‐translational
(PTMs)
such
phosphorylation,
ubiquitination,
acetylation
are
crucial
modulating
function
behavior
of
proteins.
However,
full
extent
PTM
influence
on
their
role
disease
development
remains
to
be
fully
elucidated.
This
review
addresses
gaps
offering
a
comprehensive
analysis
roles
PTMs
play
regulating
Mechanistic
insights
provided
into
how
alter
biological
processes,
contribute
cellular
function,
drive
progression.
In
addition,
current
landscape
is
examined,
highlighting
therapeutic
potential
targeting
for
precision
medicine.
By
advancing
networks,
this
seeks
facilitate
effective
strategies
inspire
future
critical
area
Clinical and Translational Medicine,
Год журнала:
2025,
Номер
15(2)
Опубликована: Фев. 1, 2025
Abstract
Therapeutic
options
for
advanced
clear
cell
renal
carcinoma
(ccRCC)
are
currently
inadequate.
Earlier
research
has
shown
that
the
enzyme
methyltransferase‐like
14
(METTL14)
can
suppress
ccRCC
development
through
modification
of
N6‐methyladenosine
(m6A).
This
study
further
explored
its
complex
biological
functions
and
underlying
molecular
mechanisms.
Here,
we
identified
zinc
finger
protein
(ZFP14)
as
a
novel
target
METTL14‐mediated
m6A,
under‐expression
was
associated
with
tumourigenesis
progression.
Detailed
investigations
revealed
METTL14
interacted
directly
3′
untranslated
region
ZFP14
mRNA,
promoting
m6A
at
two
specific
sites.
These
modifications
were
recognised
by
insulin‐like
growth
factor
2
mRNA‐binding
(IGF2BP2),
which
stabilised
enhanced
expression
mRNA.
Functionally,
METTL14/ZFP14
axis
suppressed
in
vitro
growth,
migration
invasiveness
vivo
proliferation
metastasis
cells.
potentially
regulated
numbers
transcripts,
among
matrix
metalloproteinase
1/3
(MMP1/3)
validated
to
be
under‐expressed
ZFP14.
Crucially,
signal
transducer
activator
transcription
3
(STAT3),
augmenting
K48‐linked
ubiquitination
destabilising
it
via
proteasome
pathway.
Moreover,
repressed
well
decreasing
MMP1/3
levels
under‐expressing
STAT3.
observations
confirmed
served
both
significant
tumour
suppressor
ccRCC,
shedding
light
on
cellular
operations
opening
up
possibilities
therapeutic
strategies.
Key
points
is
enhances
mRNA
stability
IGF2BP2
reader
ccRCC.
promotes
degradation
STAT3
enhancing
ubiquitination,
inhibiting
