Drug
resistance
in
cancer
cells
significantly
diminishes
treatment
efficacy,
leading
to
recurrence
and
metastasis.
A
critical
factor
contributing
this
is
the
epigenetic
alteration
of
gene
expression
via
RNA
modifications,
such
as
N6-methyladenosine
(m6A),
N1-methyladenosine
(m1A),
5-methylcytosine
(m5C),
7-methylguanosine
(m7G),
pseudouridine
(Ψ),
adenosine-to-inosine
(A-to-I)
editing.
These
modifications
are
pivotal
regulating
splicing,
translation,
transport,
degradation,
stability.
Governed
by
"writers,"
"readers,"
"erasers,"
impact
numerous
biological
processes
progression,
including
cell
proliferation,
stemness,
autophagy,
invasion,
apoptosis.
Aberrant
can
lead
drug
adverse
outcomes
various
cancers.
Thus,
targeting
modification
regulators
offers
a
promising
strategy
for
overcoming
enhancing
efficacy.
This
review
consolidates
recent
research
on
role
prevalent
resistance,
with
focus
m6A,
m1A,
m5C,
m7G,
Ψ,
A-to-I
Additionally,
it
examines
regulatory
mechanisms
linked
underscores
existing
limitations
field.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Дек. 10, 2021
Abstract
RNA
molecules
undergo
a
vast
array
of
chemical
post-transcriptional
modifications
(PTMs)
that
can
affect
their
structure
and
interaction
properties.
In
recent
years,
growing
number
PTMs
have
been
successfully
mapped
to
the
transcriptome
using
experimental
approaches
relying
on
high-throughput
sequencing.
Oxford
Nanopore
direct-RNA
sequencing
has
shown
be
sensitive
modifications.
We
developed
validated
Nanocompore,
robust
analytical
framework
identifies
from
these
data.
Our
strategy
compares
an
sample
interest
against
non-modified
control
sample,
not
requiring
training
set
allowing
use
replicates.
show
Nanocompore
detect
different
with
position
accuracy
in
vitro,
we
apply
it
profile
m
6
A
vivo
yeast
human
RNAs,
as
well
targeted
non-coding
RNAs.
confirm
our
results
orthogonal
methods
provide
novel
insights
co-occurrence
multiple
modified
residues
individual
molecules.
Abstract
Abnormal
N6-methyladenosine
(m6A)
modification
is
closely
associated
with
the
occurrence,
development,
progression
and
prognosis
of
cancer,
aberrant
m6A
regulators
have
been
identified
as
novel
anticancer
drug
targets.
Both
traditional
medicine-related
approaches
modern
discovery
platforms
used
in
an
attempt
to
develop
m6A-targeted
drugs.
Here,
we
provide
update
latest
findings
on
critical
roles
cancer
progression,
summarize
rational
sources
for
agents
from
medicines
computer-based
chemosynthetic
compounds.
This
review
highlights
potential
targeting
treatment
proposes
advantage
artificial
intelligence
(AI)
m6A-targeting
Graphical
abstract
Three
stages
discovery:
medicine-based
natural
products,
chemical
or
synthesis,
(AI)-assisted
future.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Сен. 22, 2022
RNA
modifications
have
become
hot
topics
recently.
By
influencing
processes,
including
generation,
transportation,
function,
and
metabolization,
they
act
as
critical
regulators
of
cell
biology.
The
immune
abnormality
in
human
diseases
is
also
a
research
focus
progressing
rapidly
these
years.
Studies
demonstrated
that
participate
the
multiple
biological
processes
cells,
development,
differentiation,
activation,
migration,
polarization,
thereby
modulating
responses
are
involved
some
related
diseases.
In
this
review,
we
present
existing
knowledge
functions
underlying
mechanisms
modifications,
N6-methyladenosine
(m6A),
5-methylcytosine
(m5C),
N1-methyladenosine
(m1A),
N7-methylguanosine
(m7G),
N4-acetylcytosine
(ac4C),
pseudouridine
(Ψ),
uridylation,
adenosine-to-inosine
(A-to-I)
editing,
summarize
their
roles
Via
regulating
can
pathogenesis
diseases,
such
cancers,
infection,
inflammatory
autoimmune
We
further
highlight
challenges
future
directions
based
on
knowledge.
All
all,
review
will
provide
helpful
well
novel
ideas
for
researchers
area.
Abstract
N
6
-methyladenosine
(m
A)
is
the
most
abundant
epigenetic
modification
of
RNA,
and
its
dysregulation
drives
aberrant
transcription
translation
programs
that
promote
cancer
occurrence
progression.
Although
defective
gene
regulation
resulting
from
m
A
often
affects
oncogenic
tumor-suppressing
networks,
can
also
modulate
tumor
immunogenicity
immune
cells
involved
in
anti-tumor
responses.
Understanding
this
counterintuitive
concept
aid
design
new
drugs
target
to
potentially
improve
outcomes
immunotherapies.
Here,
we
provide
an
up-to-date
comprehensive
overview
how
modifications
intrinsically
affect
alterations
cell
extrinsically
responses
microenvironment
(TME).
We
review
strategies
for
modulating
endogenous
immunity
discuss
challenge
reshaping
TME.
Strategies
include:
combining
specific
efficient
inhibitors
against
regulators
with
checkpoint
blockers;
generating
effective
programmable
gene-editing
system
enables
manipulation
individual
sites;
establishing
enhance
T
or
natural
killer
cells;
using
nanoparticles
specifically
tumor-associated
macrophages
(TAMs)
deliver
messenger
RNA
small
interfering
A-related
molecules
repolarize
TAMs,
enabling
them
remodel
The
goal
help
field
understand
shape
TME
so
better
immunotherapy
be
designed
developed.
RNA
polymerase
II
(RNA
Pol
II)
speed
or
elongation
rate,
i.e.,
the
number
of
nucleotides
synthesized
per
unit
time,
is
a
major
determinant
transcriptome
composition.
It
controls
co-transcriptional
processes
such
as
splicing,
polyadenylation,
and
transcription
termination,
thus
regulating
production
alternative
splice
variants,
circular
RNAs,
alternatively
polyadenylated
transcripts,
read-through
transcripts.
itself
regulated
in
response
to
intra-
extra-cellular
stimuli
can
turn
affect
composition
these
stimuli.
Evidence
points
potentially
important
role
modification
through
regulation
for
adaptation
cells
changing
environment,
pointing
function
cellular
physiology.
Analyzing
dynamics
may
therefore
be
central
fully
understand
physiological
processes,
development
multicellular
organisms.
Recent
findings
also
raise
possibility
that
deregulation
detrimental
participate
disease
progression.
Here,
we
review
initial
current
approaches
measure
speed,
well
providing
an
overview
factors
controlling
which
are
affected.
Finally,
discuss
cell
