Cancer Research,
Год журнала:
2021,
Номер
81(13), С. 3431 - 3440
Опубликована: Март 5, 2021
Abstract
RNA
N6-methyladenosine
(m6A)
modification
occurs
in
approximately
25%
of
mRNAs
at
the
transcriptome-wide
level.
m6A
is
regulated
by
methyltransferases
methyltransferase-like
3
(METTL3),
METTL14,
and
METTL16
(writers),
demethylases
FTO
ALKBH5
(erasers),
binding
proteins
YTHDC1–2,
YTHDF1–3,
IGF2BP1–3,
SND1
(readers).
These
are
frequently
upregulated
or
downregulated
human
cancer
tissues
often
associated
with
poor
patient
prognosis.
By
modulating
pre-mRNA
splicing,
mRNA
nuclear
export,
decay,
stability,
translation
oncogenic
tumor
suppressive
transcripts,
regulate
cell
proliferation,
survival,
migration,
invasion,
initiation,
progression,
metastasis,
sensitivity
to
anticancer
therapies.
Importantly,
small-molecule
activators
METTL3,
as
well
inhibitors
FTO,
ALKBH5,
IGF2BP1
have
recently
been
identified
shown
considerable
effects
when
administered
alone
combination
other
agents,
both
vitro
mouse
models
cancers.
Future
compound
screening
design
more
potent
selective
protein
expected
provide
novel
appropriate
for
clinical
trials
patients
harboring
aberrant
expression
protein–induced
resistance
therapy.
Signal Transduction and Targeted Therapy,
Год журнала:
2021,
Номер
6(1)
Опубликована: Фев. 21, 2021
Abstract
N
6
-methyladenosine
(m6A)
is
the
most
prevalent,
abundant
and
conserved
internal
cotranscriptional
modification
in
eukaryotic
RNAs,
especially
within
higher
cells.
m6A
modified
by
methyltransferases,
or
writers,
such
as
METTL3/14/16,
RBM15/15B,
ZC3H3,
VIRMA,
CBLL1,
WTAP,
KIAA1429,
and,
removed
demethylases,
erasers,
including
FTO
ALKBH5.
It
recognized
m6A-binding
proteins
YTHDF1/2/3,
YTHDC1/2
IGF2BP1/2/3
HNRNPA2B1,
also
known
“readers”.
Recent
studies
have
shown
that
RNA
plays
essential
role
both
physiological
pathological
conditions,
initiation
progression
of
different
types
human
cancers.
In
this
review,
we
discuss
how
methylation
influences
progressions
hematopoietic,
central
nervous
reproductive
systems.
We
will
mainly
focus
on
recent
progress
identifying
biological
functions
underlying
molecular
mechanisms
methylation,
its
regulators
downstream
target
genes,
during
cancer
above
propose
process
offer
potential
targets
for
therapy
future.
N6-methyladenosine
(m6A)
is
methylation
that
occurs
in
the
N6-position
of
adenosine,
which
most
prevalent
internal
modification
on
eukaryotic
mRNA.
Accumulating
evidence
suggests
m6A
modulates
gene
expression,
thereby
regulating
cellular
processes
ranging
from
cell
self-renewal,
differentiation,
invasion
and
apoptosis.
M6A
installed
by
methyltransferases,
removed
demethylases
recognized
reader
proteins,
regulate
RNA
metabolism
including
translation,
splicing,
export,
degradation
microRNA
processing.
Alteration
levels
participates
cancer
pathogenesis
development
via
expression
tumor-related
genes
like
BRD4,
MYC,
SOCS2
EGFR.
In
this
review,
we
elaborate
recent
advances
research
enzymes.
We
also
highlight
underlying
mechanism
progression.
Finally,
review
corresponding
potential
targets
therapy.
N6-methyladenosine
(m6A)
is
identified
as
the
most
common,
abundant
and
conserved
internal
transcriptional
modification,
especially
within
eukaryotic
messenger
RNAs
(mRNAs).
M6A
modification
installed
by
m6A
methyltransferases
(METTL3/14,
WTAP,
RBM15/15B
KIAA1429,
termed
"writers"),
reverted
demethylases
(FTO
ALKBH5,
"erasers")
recognized
binding
proteins
(YTHDF1/2/3,
IGF2BP1
HNRNPA2B1,
"readers").
Acumulating
evidence
shows
that,
RNA
methylation
has
an
outsize
effect
on
production/metabolism
participates
in
pathogenesis
of
multiple
diseases
including
cancers.
Until
now,
molecular
mechanisms
underlying
various
tumors
have
not
been
comprehensively
clarified.
In
this
review,
we
mainly
summarize
recent
advances
biological
function
modifications
human
cancer
discuss
potential
therapeutic
strategies.
Nucleic Acids Research,
Год журнала:
2020,
Номер
48(7), С. 3816 - 3831
Опубликована: Янв. 22, 2020
Abstract
N
6-Methyladenosine
(m6A)
is
the
most
abundant
RNA
modification
in
mammal
mRNAs
and
increasing
evidence
suggests
key
roles
of
m6A
human
tumorigenesis.
However,
whether
m6A,
especially
its
‘reader’
YTHDF1,
targets
a
gene
involving
protein
translation
thus
affects
overall
production
cancer
cells
largely
unexplored.
Here,
using
multi-omics
analysis
for
ovarian
cancer,
we
identified
novel
mechanism
EIF3C,
subunit
initiation
factor
EIF3,
as
direct
target
YTHDF1.
YTHDF1
augments
EIF3C
an
m6A-dependent
manner
by
binding
to
m6A-modified
mRNA
concomitantly
promotes
translational
output,
thereby
facilitating
tumorigenesis
metastasis
cancer.
frequently
amplified
up-regulation
associated
with
adverse
prognosis
patients.
Furthermore,
but
not
abundance
increased
positively
correlates
expression
patients,
suggesting
more
relevant
role
Collectively,
identify
YTHDF1-EIF3C
axis
critical
progression
which
can
serve
develop
therapeutics
treatment.
