Biotechnology Journal,
Journal Year:
2024,
Volume and Issue:
19(4)
Published: April 1, 2024
Due
to
their
high-quality
characteristics,
Chinese
hamster
ovary
(CHO)
cells
have
become
the
most
widely
used
and
reliable
host
for
production
of
recombinant
therapeutic
proteins
in
biomedical
field.
Previous
studies
shown
that
m6A
reader
YTHDF3,
which
contains
YTH
domain,
can
affect
a
variety
biological
processes
by
regulating
translation
stability
target
mRNAs.
This
study
investigates
effect
YTHDF3
on
transgenic
CHO
cells.
The
results
indicate
stable
overexpression
significantly
enhances
protein
expression
without
affecting
cell
growth.
Transcriptome
sequencing
indicated
several
genes,
including
initiation
factor,
extension
ribosome
assembly
were
upregulated
overexpressing
YTHDF3.
In
addition,
cycloheximide
experiments
confirmed
enhanced
transgene
promoting
conclusion,
findings
this
provide
novel
approach
mammalian
engineering
increase
productivity
m6A.
Cancer Science,
Journal Year:
2024,
Volume and Issue:
115(8), P. 2588 - 2601
Published: May 29, 2024
Abstract
Insufficient
understanding
about
the
immune
evasion
mechanism
leads
to
inability
in
predicting
current
immunotherapy
effects
clear
cell
renal
carcinoma
(ccRCC)
and
sensitizing
ccRCC
immunotherapy.
RNA
binding
proteins
(RBPs)
can
promote
tumor
progression
evasion.
However,
research
on
RBPs,
particularly
m6A
reader
YTHDF3,
development
is
limited.
In
this
study,
we
found
that
YTHDF3
level
was
downregulated
an
independent
prognostic
biomarker
for
ccRCC.
Decreased
expression
correlated
with
malignancy,
evasion,
poor
response
anti‐programmed
death
ligand
1
(PD‐L1)/CTLA‐4
overexpression
restrained
PD‐L1
expression,
CD8
+
T
infiltration
activities
vivo,
indicating
its
inhibitory
role
Mechanistically,
WT
have
phase
separation
characteristics
suppress
malignancy
Whereas
mutant,
which
disrupted
separation,
abolished
function.
enhanced
degradation
of
target
mRNA
HSPA13
by
recruiting
DDX6,
resulting
downregulation
downstream
checkpoint
PD‐L1.
restored
suppressed
overexpression.
all,
our
results
identify
a
new
model
regulating
through
separation.
Advanced Science,
Journal Year:
2024,
Volume and Issue:
11(44)
Published: Oct. 8, 2024
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
Biomedicine & Pharmacotherapy,
Journal Year:
2023,
Volume and Issue:
167, P. 115477 - 115477
Published: Sept. 9, 2023
Cancer
therapy
resistance
(CTR)
is
the
development
of
cancer
to
multiple
therapeutic
strategies,
which
severely
affects
clinical
response
and
leads
progression,
recurrence,
metastasis.
N6-methyladenosine
(m6A)
has
been
identified
as
most
common,
abundant,
conserved
internal
transcriptional
alterations
RNA
modifications,
regulating
splicing,
translation,
stabilization,
degradation,
gene
expression,
involved
in
progression
a
variety
diseases,
including
cancer.
Recent
studies
have
shown
that
m6A
modifications
play
critical
role
both
especially
reversing
CTR.
Although
great
potential
CTR,
specific
molecular
mechanisms
are
not
fully
elucidated.
In
this
review,
we
summarize
modification
addition,
update
recent
advances
natural
products
from
Traditional
Chinese
Medicines
(TCM)
small-molecule
lead
compounds
targeting
discuss
implications
these
inhibitors
regulators
combinations
with
other
therapies
improve
efficacy
overcome
International Journal of Biological Sciences,
Journal Year:
2025,
Volume and Issue:
21(3), P. 1187 - 1201
Published: Jan. 13, 2025
Pancreatic
cancer
(PC),
known
as
the
"king
of
cancers,"
is
characterized
by
an
exceptionally
low
five-year
survival
rate,
posing
a
formidable
challenge
to
global
public
health.
N6-methyladenosine
(m6A)
methylation
prevalent
across
various
stages
eukaryotic
RNA
expression,
including
splicing,
maturation,
stability,
translation,
and
localization,
represents
pivotal
mechanism
epigenetic
regulation.
m6A
influences
tumor
initiation
progression
modulating
post-transcriptional
processes,
playing
critical
role
in
sustaining
cell
stemness,
promoting
proliferation,
mediating
drug
resistance.
Extensive
research
underscores
substantial
contribution
modifications
PC
development.
However,
multiplicity
regulators
their
intricate
mechanisms
action
complicate
landscape.
This
review
aims
deepen
understanding
m6A's
delineating
its
involvement
four
key
areas
tumorigenesis:
hypoxic
microenvironment,
metabolic
reprogramming,
immune
resistance
mechanisms.
Additionally,
addresses
emerging
frontier
interactions
with
non-coding
RNAs
(ncRNAs),
offering
insights
into
potential
therapeutic
prognostic
applications
treatment
prognosis
prediction
PC.
ABSTRACT
Epitranscriptomic
modification
of
RNA
is
an
important
layer
regulation
for
gene
expression.
modifications
come
in
many
flavors
and
generate
a
complex
tapestry
regulatory
network.
Here,
we
focus
on
two
major
modifications,
one
rRNA
(2′O
Methylation)
another
mRNA
(N
6
‐Methyladenosine
[m
A])
their
impact
translation.
The
2′O
methyl
group
addition
the
ribose
sugar
plays
critical
role
folding,
ribosome
assembly,
its
interaction
with
binding
proteins.
Differential
methylation
these
sites
contributes
to
heterogeneity
generates
potential
“specialized
ribosomes.”
Specialized
ribosomes
are
proposed
play
variety
roles
maintaining
pluripotency,
lineage
specification,
compartmentalized
activity‐mediated
translation
neurons.
m
A
modification,
other
hand,
determines
stability,
transport,
subclasses
mRNA.
dynamic
nature
owing
localization
activity
writers,
readers,
erasers
makes
it
powerful
tool
spatiotemporal
While
substantial
information
has
accumulated
abundance
functional
consequences
still
understudied.
In
this
article,
review
literature
constructing
body
our
understanding
outcome
general
nervous
system
particular.
We
also
explore
possibility
how
may
collaborate
modulating
provoke
thought
integrate
functions
multiple
epitranscriptome
modifications.
Cell & Bioscience,
Journal Year:
2025,
Volume and Issue:
15(1)
Published: Feb. 22, 2025
Abstract
N6-methyladenosine
(m6A),
the
most
prevalent
RNA
modification
in
eukaryotes,
plays
a
critical
role
development
and
progression
of
various
diseases,
including
cancer,
through
its
regulation
degradation,
stabilization,
splicing,
cap-independent
translation.
Emerging
evidence
underscores
significant
m6A
modifications
both
pro-tumorigenic
anti-tumorigenic
immune
responses.
In
this
review,
we
provide
comprehensive
overview
examine
relationship
between
regulators
cancer
Additionally,
summarize
recent
advances
understanding
how
influence
tumor
responses
by
directly
modulating
cells
(e.g.,
dendritic
cells,
tumor-associated
macrophages,
T
cells)
indirectly
affecting
via
mechanisms
such
as
cytokine
chemokine
regulation,
modulation
cell
surface
molecules,
metabolic
reprogramming.
Furthermore,
explore
potential
synergistic
effects
targeting
combination
with
checkpoint
inhibitor
(ICI)
therapies.
Together,
review
consolidates
current
knowledge
on
m6A-mediated
immunity,
offering
insights
into
deeper
these
may
identify
patients
who
are
likely
to
benefit
from
immunotherapies.
Molecular Medicine,
Journal Year:
2025,
Volume and Issue:
31(1)
Published: Feb. 25, 2025
Abstract
Background
Endometriosis
(EMs)
is
a
condition
characterized
by
the
growth
of
endometrial
tissue
outside
uterine
cavity.
Although
this
benign,
it
has
cancer-like
features.
N6-methyladenosine
(m6A)
common
RNA
modification
involved
in
diverse
biological
processes,
but
its
role
EMs
remains
unclear.
Methods
A
human
stromal
cell
line
(HESCs),
primary
eutopic
cells
(Eu-ESCs),
ectopic
(Ec-ESCs),
and
clinical
samples
were
used
study.
colorimetric
assay
was
to
measure
methylation
levels
mouse
samples.
Functional
assays
(CCK-8,
EdU,
Transwell,
wound
healing)
evaluate
phenotypic
changes.
m6A
immunoprecipitation
sequencing
(MeRIP-seq)
identified
downstream
targets.
Mechanistic
studies
conducted
via
qRT‒PCR,
Western
blot,
(RIP),
dual-luciferase
reporter,
stability
assays.
Results
We
detected
aberrantly
low
within
endometriotic
lesions,
which
attributed
increased
expression
eraser
fat
mass
obesity-associated
protein
(FTO).
Notably,
estrogen
inflammatory
factors,
are
recognized
as
pathogenic
agents
amplify
FTO
while
suppressing
levels.
In
vitro
experiments
demonstrated
that
overexpression
leads
reduction
concomitantly
promotes
their
proliferation,
migration,
invasion.
Furthermore,
both
genetic
deletion
Fto
chemical
inhibition
impeded
lesions
vivo.
By
utilizing
m6A-seq,
we
GEF-H1
(a
Rho
guanine
nucleotide
exchange
factor)
pivotal
target
FTO.
Specifically,
diminished
at
certain
site
3'UTR
YTH
RNA-binding
F1
(YTHDF1)-dependent
manner,
thereby
activating
RhoA
pathway.
Subsequent
revealed
mediates
effects
promoting
migration
Conclusions
This
study
decreases
level
,
increasing
stability,
turn
activates
GEF-H1-RhoA
pathway
promote
invasion
cells,
inducing
EMs.
Our
findings
suggest
potential
therapeutic
avenues
for
targeting
alleviate
progression.
