Biomarker Research,
Год журнала:
2023,
Номер
11(1)
Опубликована: Янв. 17, 2023
Abstract
YTHDF1
is
a
well-characterized
m6A
reader
protein
that
essential
for
translation,
stem
cell
self-renewal,
and
embryonic
development.
regulates
target
gene
expression
by
diverse
molecular
mechanisms,
such
as
promoting
translation
or
modulating
the
stability
of
mRNA.
The
cellular
levels
are
precisely
regulated
complicated
transcriptional,
post-transcriptional,
post-translational
network.
Very
solid
evidence
supports
pivotal
role
in
development
human
cancer
progression.
In
this
review,
we
discuss
how
influences
both
physiological
pathological
biology
central
nervous,
reproductive
immune
systems.
Therefore
focus
on
some
relevant
aspects
regulatory
played
expression,
complex
networking:
development,
cancers
We
propose
promising
future
biomarker
detection,
progression,
prognosis.
Targeting
holds
therapeutic
potential,
overexpression
associated
with
tumor
resistance
to
chemotherapy
immunotherapy.
Seminars in Cancer Biology,
Год журнала:
2023,
Номер
92, С. 16 - 27
Опубликована: Март 24, 2023
Excess
body
weight
is
a
global
health
problem
due
to
sedentary
lifestyle
and
unhealthy
diet,
affecting
2
billion
population
worldwide.
Obesity
major
risk
factor
for
metabolic
diseases.
Notably,
the
of
obesity
largely
depends
on
distribution,
which
visceral
adipose
tissues
but
not
subcutaneous
fats
are
closely
associated
with
comorbidities,
including
type
diabetes,
non-alcoholic
fatty
liver
disease,
cardiovascular
disease
certain
types
cancer.
Latest
multi-omics
mechanistical
studies
reported
crucial
involvement
genetic
epigenetic
alterations,
adipokines
dysregulation,
immunity
changes,
imbalance
white
brown
tissues,
gut
microbial
dysbiosis
in
mediating
pathogenic
association
between
comorbidities.
In
this
review,
we
explore
epidemiology
excess
up-to-date
mechanism
how
lead
chronic
complications.
We
also
examine
utilization
fat
measurement
as
an
accurate
clinical
parameter
assessment
healthy
individuals
outcome
prediction
obese
subjects.
addition,
current
approaches
prevention
treatment
its
related
comorbidities
further
discussed.
Cancer
therapy
resistance
is
the
main
cause
of
cancer
treatment
failure.
The
mechanism
a
hot
topic
in
epigenetics.
As
one
most
common
RNA
modifications,
N6-methyladenosine
(m6A)
involved
various
processes
metabolism,
such
as
stability,
splicing,
transcription,
translation,
and
degradation.
A
large
number
studies
have
shown
that
m6A
methylation
regulates
proliferation
invasion
cells,
but
role
unclear.
In
this
review,
we
summarized
research
progress
related
to
regulating
cancers.
Cell Reports Medicine,
Год журнала:
2023,
Номер
4(8), С. 101144 - 101144
Опубликована: Авг. 1, 2023
Non-alcoholic
fatty
liver
disease
(NAFLD)
is
an
emerging
risk
factor
of
hepatocellular
carcinoma
(HCC).
However,
the
mechanism
and
target
therapy
NAFLD-HCC
are
still
unclear.
Here,
we
identify
that
N6-methyladenosine
(m6A)
methyltransferase
METTL3
promotes
NAFLD-HCC.
Hepatocyte-specific
Mettl3
knockin
exacerbated
formation,
while
knockout
exerted
opposite
effect
in
mice.
Single-cell
RNA
sequencing
revealed
suppressed
antitumor
immune
response
by
reducing
granzyme
B
(GZMB+)
interferon
gamma-positive
(IFN-γ+)
CD8+
T
cell
infiltration,
thereby
facilitating
escape.
Mechanistically,
mediates
sterol
regulatory
element-binding
protein
(SREBP)
cleavage-activating
(SCAP)
mRNA
m6A
to
promote
its
translation,
leading
activation
cholesterol
biosynthesis.
This
enhanced
secretion
cholesteryl
esters
impair
function
tumor
microenvironment.
Targeting
single-guide
RNA,
nanoparticle
small
interfering
(siRNA),
or
pharmacological
inhibitor
(STM2457)
combination
with
anti-programmed
death
1
(PD-1)
synergized
reinvigorate
cytotoxic
cells
mediate
regression.
Together,
a
therapeutic
NAFLD-HCC,
especially
conjunction
checkpoint
blockade
(ICB)
therapy.
Gastroenterology,
Год журнала:
2023,
Номер
165(2), С. 445 - 462
Опубликована: Май 9, 2023
Immune
checkpoint
blockade
therapy
benefits
only
a
small
subset
of
patients
with
colorectal
cancer
(CRC),
and
identification
CRC-intrinsic
events
modulating
immune
efficacy
is
an
unmet
need.
We
found
that
AlkB
homolog
5
(ALKBH5),
RNA
N
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Янв. 17, 2023
Abstract
The
recently
described
role
of
RNA
methylation
in
regulating
immune
cell
infiltration
into
tumors
has
attracted
interest,
given
its
potential
impact
on
immunotherapy
response.
YTHDF1
is
a
versatile
and
powerful
m6A
reader,
but
the
understanding
evasion
limited.
Here,
we
reveal
that
tumor-intrinsic
drives
checkpoint
inhibitor
(ICI)
resistance.
Additionally,
deficiency
converts
cold
responsive
hot
tumors,
which
improves
ICI
efficacy.
Mechanistically,
inhibits
translation
lysosomal
genes
limits
proteolysis
major
histocompatibility
complex
class
I
(MHC-I)
antigens,
ultimately
restoring
tumor
surveillance.
In
addition,
design
system
for
exosome-mediated
CRISPR/Cas9
delivery
to
target
vivo,
resulting
depletion
antitumor
activity.
Our
findings
elucidate
driving
underlying
mechanism.
Trends in Pharmacological Sciences,
Год журнала:
2023,
Номер
44(6), С. 335 - 353
Опубликована: Апрель 15, 2023
Specific
RNA
sequences
modified
by
a
methylated
adenosine,
N6-methyladenosine
(m6A),
contribute
to
the
post-transcriptional
regulation
of
gene
expression.
The
quantity
m6A
in
is
orchestrated
enzymes
that
write
and
erase
it,
while
its
effects
are
mediated
proteins
bind
read
this
modification.
Dysfunction
regulatory
process
has
been
linked
human
disease.
Although
initial
focus
on
pharmacological
targeting
writer
eraser
enzymes,
interest
reader
challenged
lack
clear
understanding
their
functional
roles
molecular
mechanisms
action.
Readers
m6A-modified
(m6A-RNA)
–
YTH
(YT521-B
homology)
domain-containing
protein
family
paralogs
1–3
(YTHDF1–3,
referred
here
as
DF1–DF3)
emerging
therapeutic
targets
links
pathological
processes
such
cancer
inflammation
regulating
m6A-RNA
fate
become
clear.
We
provide
an
updated
modes
action
DF1–DF3
review
structures
unlock
insights
into
drug
design
approaches
for
DF
paralog-selective
inhibition.
