Research Square (Research Square),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Aug. 19, 2022
Abstract
It
has
been
reported
that
N
6
-methyladenosine
(m
A)
modification
is
mainly
involved
in
clear-cell
renal
cell
carcinoma
(ccRCC)
tumorigenesis.
However,
the
regulatory
mechanisms
of
m
A
reader
IGF2BP1
ccRCC
tumor
energy
metabolism
are
currently
unknown.
Results
showed
exhibited
significantly
higher
expression
cells.
Functionally,
results
by
gainloss
functional
assay
indicated
promoted
glucolytic
characteristics,
including
glucose
uptake,
lactate
production
and
extracellular
acidification
rate
(ECAR).
Mechanistically,
recognizes
modified
sites
on
LDHA
mRNA
enhances
its
stability,
thereby
accelerating
metabolism.
Thus,
our
work
reveals
a
novel
facet
promotes
stability
highlights
importance
as
readers
post-transcriptional
gene
regulation.
Experimental & Molecular Medicine,
Journal Year:
2024,
Volume and Issue:
56(1), P. 156 - 167
Published: Jan. 4, 2024
Abstract
Osteoarthritis
(OA)
is
the
most
common
form
of
arthritis.
However,
exact
pathogenesis
remains
unclear.
Emerging
evidence
shows
that
N6-methyladenosine
(m
6
A)
modification
may
have
an
important
role
in
OA
pathogenesis.
This
study
aimed
to
investigate
m
A
writers
and
underlying
mechanisms
osteoarthritic
cartilage.
Among
methyltransferases,
Wilms
tumor
1-associated
protein
(WTAP)
expression
significantly
differed
clinical
WTAP
regulated
extracellular
matrix
(ECM)
degradation,
inflammation
antioxidation
human
chondrocytes.
Mechanistically,
relative
downstream
targets
cartilage
were
assessed
by
methylated
RNA
immunoprecipitation
sequencing
(MeRIP-seq)
sequencing,
which
indicated
frizzled-related
(FRZB),
a
secreted
Wnt
antagonist,
was
abnormally
decreased
accompanied
high
In
vitro
dysregulated
had
positive
effects
on
β-catenin
targeting
FRZB,
finally
contributed
injury
phenotype
Intra-articular
injection
adeno-associated
virus-WTAP
alleviated
progression
mouse
model,
while
this
protective
effect
could
be
reversed
application
Wnt/β-catenin
activator.
summary,
revealed
WTAP-dependent
pathway
activation
through
post-transcriptional
regulation
FRZB
mRNA,
thus
providing
potentially
effective
therapeutic
strategy
for
treatment.
International Journal of Biological Sciences,
Journal Year:
2023,
Volume and Issue:
19(5), P. 1616 - 1632
Published: Jan. 1, 2023
Cancer
progression
depends
on
the
communication
between
tumor
cells
and
microenvironment.
Cancer-associated
fibroblasts
(CAFs)
are
a
major
component
of
stromal
cells.
CAFs
promote
cancer
metastasis;
however,
it
has
not
been
evaluated
whether
N6-methyladenosine
(m6A)
modification
is
responsible
for
CAFs'
role
in
metastasis.
In
present
study,
we
found
that
promoted
migration
invasion
non-small
cell
lung
(NSCLC)
by
elevating
m6A
NSCLC
Methyltransferase-like
3
(METTL3)
mediated
effect
modification,
was
regulated
CAFs-secreted
vascular
endothelial
growth
factor
A
(VEGFA).
METTL3
knockdown
dramatically
inhibited
invasion,
suppressed
vivo.
Database
analysis
revealed
associated
with
poor
prognosis
cancer.
The
mechanism
study
showed
increased
level
RAC3
mRNA,
resulting
stability
translation
mRNA.
promoting
via
AKT/NF-κB
pathway.
This
established
CAF-METTL3-RAC3
modification-dependent
regulation
system
metastasis,
suggesting
potential
candidates
metastasis
treatment.
Journal of Translational Medicine,
Journal Year:
2023,
Volume and Issue:
21(1)
Published: May 22, 2023
Abstract
Background
Disruption
of
N6
methyl
adenosine
(m6A)
modulation
hampers
gene
expression
and
cellular
functions,
leading
to
various
illnesses.
However,
the
role
m6A
modification
in
osteoarthritis
(OA)
synovitis
remains
unclear.
This
study
aimed
explore
patterns
regulators
OA
synovial
cell
clusters
identify
key
that
mediate
macrophage
phenotypes.
Methods
The
synovium
were
illustrated
by
analyzing
bulk
RNA-seq
data.
Next,
we
built
an
LASSO-Cox
regression
prediction
model
core
regulators.
Potential
target
genes
these
identified
data
from
RM2target
database.
A
molecular
functional
network
based
on
their
was
constructed
using
STRING
Single-cell
collected
verify
effects
clusters.
Conjoint
analyses
single-cell
performed
validate
correlation
between
regulators,
clusters,
disease
conditions.
After
IGF2BP3
screened
as
a
potential
modulator
macrophages,
level
tested
its
functions
further
overexpression
knockdown
vitro.
Results
showed
aberrant
Based
well-fitting
comprising
six
factors
(FTO,
YTHDC1,
METTL5,
IGF2BP3,
ZC3H13,
HNRNPC).
indicated
closely
associated
with
phenotypic
alterations.
Among
reader
mediator.
Finally,
upregulation
verified
synovium,
which
promoted
M1
polarization
inflammation.
Conclusions
Our
findings
revealed
highlighted
association
enhanced
inflammation
providing
novel
targets
for
diagnosis
treatment.
Arthritis Research & Therapy,
Journal Year:
2023,
Volume and Issue:
25(1)
Published: April 1, 2023
Abstract
Objectives
Increasing
evidence
have
demonstrated
the
N6-methyladenosine
(m
6
A)
plays
critical
roles
in
osteoarthritis
(OA)
progression,
but
role
of
m
A
OA
has
not
been
completely
illuminated.
Herein,
we
investigated
function
and
underlying
mechanism
demethylase
fat
mass
obesity-associated
protein
(
FTO
)
progression.
Materials
methods
The
expression
was
detected
mice
cartilage
tissues
lipopolysaccharide
(LPS)-stimulated
chondrocytes.
Gain-of-function
assays
used
to
evaluate
injury
vitro
vivo.
miRNA-sequencing,
RNA-binding
immunoprecipitation
(RIP),
luciferase
reporter
assay,
pri-miRNA
processing
were
conducted
confirm
that
modulated
pri-miR-3591
process
an
m6A-dependent
manner
then
binding
sites
miR-3591-5p
with
PRKAA2
.
Results
outstandingly
downregulated
LPS-stimulated
chondrocytes
tissues.
overexpression
enhanced
proliferation,
suppressed
apoptosis,
decreased
degradation
extracellular
matrix
LPS-induced
chondrocytes,
whereas
knockdown
contributed
opposite
effects.
In
vivo
animal
experiments
showed
markedly
alleviated
injury.
Mechanically,
-mediated
m6A
demethylation
leaded
a
maturation
block
,
which
relieved
inhibitory
effect
on
promoted
increase
thereby
alleviating
damage.
Conclusions
Our
results
attested
damage
by
mediating
/
axis,
provided
fresh
insights
into
therapeutic
strategies
for
OA.
Journal of Translational Medicine,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: Feb. 14, 2024
Abstract
Skeletal
system
disease
(SSD)
is
defined
as
a
class
of
chronic
disorders
skeletal
with
poor
prognosis
and
causes
heavy
economic
burden.
m6A,
methylation
at
the
N6
position
adenosine
in
RNA,
reversible
dynamic
modification
posttranscriptional
mRNA.
Evidences
suggest
that
m6A
modifications
play
crucial
role
regulating
biological
processes
all
kinds
diseases,
such
malignancy.
Recently
studies
have
revealed
most
abundant
epigentic
modification,
involved
progression
SSD.
However,
function
SSD
not
fully
illustrated.
Therefore,
make
clear
relationship
between
pathogenesis
might
provide
novel
sights
for
prevention
targeted
treatment
This
article
will
summarize
recent
advances
regulation
SSD,
including
osteoporosis,
osteosarcoma,
rheumatoid
arthritis
osteoarthritis,
discuss
potential
clinical
value,
research
challenge
future
prospect
PeerJ,
Journal Year:
2023,
Volume and Issue:
11, P. e14591 - e14591
Published: Jan. 18, 2023
Emerging
articles
have
reported
that
N6-methyladenosine
(m6A)
modification
is
mainly
involved
in
clear-cell
renal
cell
carcinoma
(ccRCC)
tumorigenesis.
However,
the
regulatory
mechanisms
of
m6A
reader
IGF2BP1
ccRCC
tumor
energy
metabolism
are
currently
unknown.
Results
showed
exhibited
significantly
higher
expression
cells.
Functionally,
results
by
gain/loss
functional
assays
indicated
promoted
glycolytic
characteristics,
including
glucose
uptake,
lactate
production
and
extracellular
acidification
rate
(ECAR).
Mechanistically,
recognized
modified
sites
on
LDHA
mRNA
enhanced
its
stability,
thereby
accelerating
metabolism.
Thus,
our
work
reveals
a
novel
facet
stability
highlighted
importance
as
readers
post-transcriptional
gene
regulation.
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: June 9, 2023
Osteoarthritis
is
non-inflammatory
degenerative
joint
arthritis,
which
exacerbates
disability
in
elder
persons.
The
molecular
mechanisms
of
osteoarthritis
are
elusive.
Ubiquitination,
one
type
post-translational
modifications,
has
been
demonstrated
to
accelerate
or
ameliorate
the
development
and
progression
via
targeting
specific
proteins
for
ubiquitination
determining
protein
stability
localization.
Ubiquitination
process
can
be
reversed
by
a
class
deubiquitinases
deubiquitination.
In
this
review,
we
summarize
current
knowledge
regarding
multifaceted
role
E3
ubiquitin
ligases
pathogenesis
osteoarthritis.
We
also
describe
insight
into
processes.
Moreover,
highlight
multiple
compounds
that
target
influence
progression.
discuss
challenge
future
perspectives
modulation
expression
enhancement
therapeutic
efficacy
patients.
conclude
modulating
deubiquitination
could
alleviate
achieve
better
treatment
outcomes
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: March 15, 2023
RNA
modifications
in
eukaryotic
cells
have
emerged
as
an
exciting
but
under-explored
area
recent
years
and
are
considered
to
be
associated
with
many
human
diseases.
While
several
studies
been
published
relating
m6A
osteoarthritis
(OA),
we
only
limited
knowledge
of
other
kinds
modifications.
Our
study
investigated
eight
modifiers'
specific
roles
OA
including
A-to-I,
APA,
m5C,
m6A,
m7G,
mcm5s2U,
Nm
Ψ
together
their
relationship
immune
infiltration.
