N6-methyladenosine
(m6A)
is
one
of
the
most
common
RNA
modifications
in
eukaryotes,
mainly
messenger
(mRNA).
Increasing
evidence
shows
that
m6A
methylation
modification
acts
an
essential
role
various
physiological
and
pathological
bioprocesses.
Noncoding
RNAs
(ncRNAs),
including
miRNAs,
lncRNAs
circRNAs,
are
known
to
participate
regulating
cell
differentiation,
angiogenesis,
immune
response,
inflammatory
response
carcinogenesis.
regulators,
such
as
METTL3,
ALKBH5
IGF2BP1
have
been
reported
execute
a
m6A-dependent
ncRNAs
involved
Meanwhile,
can
target
or
modulate
regulators
influence
cancer
development.
In
this
review,
we
provide
insight
into
interplay
between
cancer.
Theranostics,
Год журнала:
2020,
Номер
10(19), С. 8721 - 8743
Опубликована: Янв. 1, 2020
Over
the
past
few
decades,
substantial
evidence
has
convincingly
revealed
existence
of
cancer
stem
cells
(CSCs)
as
a
minor
subpopulation
in
cancers,
contributing
to
an
aberrantly
high
degree
cellular
heterogeneity
within
tumor.
CSCs
are
functionally
defined
by
their
abilities
self-renewal
and
differentiation,
often
response
cues
from
microenvironment.
Biological
phenotypes
regulated
integrated
transcriptional,
post-transcriptional,
metabolic,
epigenetic
regulatory
networks.
contribute
tumor
progression,
therapeutic
resistance,
disease
recurrence
through
sustained
proliferation,
invasion
into
normal
tissue,
promotion
angiogenesis,
evasion
immune
system,
resistance
conventional
anticancer
therapies.
Therefore,
elucidation
molecular
mechanisms
that
drive
cell
maintenance,
plasticity,
will
enhance
our
ability
improve
effectiveness
targeted
therapies
for
CSCs.
In
this
review,
we
highlight
key
features
regulate
CSC
function
initiation,
therapy
resistance.
We
discuss
factors
such
quiescence,
induction
epithelial-to-mesenchymal
transition
(EMT),
DNA
damage-induced
death.
evaluate
approaches
eliminating
therapy-resistant
subpopulations,
including
drugs
target
signaling
pathways
surface
markers,
viral
therapies,
awakening
quiescent
CSCs,
immunotherapy.
also
assess
impact
new
technologies,
single-cell
sequencing
CRISPR-Cas9
screening,
on
investigation
biological
properties
Moreover,
challenges
remain
be
addressed
coming
years,
experimental
investigating
obstacles
targeting
ACS Central Science,
Год журнала:
2021,
Номер
7(5), С. 748 - 756
Опубликована: Апрель 6, 2021
The
novel
coronavirus
SARS-CoV-2,
the
cause
of
COVID-19
pandemic,
has
inspired
one
most
efficient
vaccine
development
campaigns
in
human
history.
A
key
aspect
mRNA
vaccines
is
use
modified
nucleobase
N1-methylpseudouridine
(m1Ψ)
to
increase
their
effectiveness.
In
this
Outlook,
we
summarize
and
function
m1Ψ
synthetic
mRNAs.
By
demystifying
how
a
element
within
these
medicines
works,
aim
foster
understanding
highlight
future
opportunities
for
chemical
innovation.
The
importance
of
mRNA
methylation
erased
by
ALKBH5
in
biogenesis,
decay,
and
translation
control
is
an
emerging
research
focus.
Ectopically
activated
YAP
associated
with
the
development
many
human
cancers.
However,
mechanism
whereby
regulates
expression
activity
to
inhibit
NSCLC
tumor
growth
metastasis
not
clear.Protein
transcript
interactions
were
analyzed
normal
lung
cell
cells.
Gene
was
evaluated
qPCR
reporter
assays.
Protein
levels
determined
immunochemical
approaches.
Nucleic
acid
status
immunoprecipitation.
Cell
behavior
standard
biochemical
tests.
m6A
modification
MeRIP.Our
results
show
that
negatively
correlated
plays
opposite
role
regulation
cellular
proliferation,
invasion,
migration,
EMT
reduced
YAP.
YTHDF3
combined
pre-mRNA
depending
on
modification.
YTHDF1
YTHDF2
competitively
interacted
m6A-independent
manner
regulate
expression.
facilitated
decay
via
AGO2
system,
whereas
promoted
interacting
eIF3a;
both
these
activities
are
regulated
Furthermore,
decreased
regulating
miR-107/LATS2
axis
HuR-dependent
manner.
Further,
inhibited
vivo
reducing
YAP.The
presented
findings
suggest
demethylase
inhibits
YTHDFs-mediated
inhibiting
miR-107/LATS2-mediated
NSCLC.
Moreover,
effective
inhibition
might
constitute
a
potential
treatment
strategy
for
cancer.
Annals of the Rheumatic Diseases,
Год журнала:
2021,
Номер
81(1), С. 85 - 97
Опубликована: Окт. 27, 2021
Objective
The
aim
of
the
study
was
to
investigate
role
and
regulatory
mechanisms
fibroblast-like
synoviocytes
(FLSs)
their
senescence
in
progression
osteoarthritis
(OA).
Methods
Synovial
tissues
from
normal
patients
with
OA
were
collected.
Synovium
FLS
analysed
by
immunofluorescence
western
blotting.
methyltransferase-like
3
(METTL3)
autophagy
regulation
explored
using
N6-methyladenosine
(m
6
A)-methylated
RNA
immunoprecipitation
assays.
Mice
subjected
destabilisation
medial
meniscus
(DMM)
surgery
intra-articularly
injected
or
without
pAAV9
loaded
small
interfering
(siRNA)
targeting
METTL3.
Histological
analysis
performed
determine
cartilage
damage.
Results
Senescent
FLSs
markedly
increased
mouse
models.
We
determined
that
impaired
occurred
OA-FLS,
resulting
upregulation
senescence-associated
secretory
phenotype
(SASP).
Re-establishment
reversed
senescent
suppressing
GATA4.
Further,
we
observed
for
first
time
excessive
m
A
modification
negatively
regulated
OA-FLS.
Mechanistically,
METTL3-mediated
decreased
expression
autophagy-related
7,
an
E-1
enzyme
crucial
formation
autophagosomes,
attenuating
its
stability.
Silencing
METTL3
enhanced
autophagic
flux
inhibited
SASP
Intra-articular
injection
synovium-targeted
siRNA
suppressed
cellular
propagation
joints
ameliorated
DMM-induced
destruction.
Conclusions
Our
revealed
important
progression.
Targeted
inhibition
could
alleviate
limit
development
experimental
animal
models,
providing
a
potential
strategy
therapy.
