Development of m6A/m5C/m1A regulated lncRNA signature for prognostic prediction, personalized immune intervention and drug selection in LUAD
Chao Ma,
No information about this author
Zhuoyu Gu,
No information about this author
Yang Yang
No information about this author
et al.
Journal of Cellular and Molecular Medicine,
Journal Year:
2024,
Volume and Issue:
28(8)
Published: April 1, 2024
Abstract
Research
indicates
that
there
are
links
between
m6A,
m5C
and
m1A
modifications
the
development
of
different
types
tumours.
However,
it
is
not
yet
clear
if
these
involved
in
prognosis
LUAD.
The
TCGA‐LUAD
dataset
was
used
as
for
signature
training,
while
validation
cohort
created
by
amalgamating
publicly
accessible
GEO
datasets
including
GSE29013,
GSE30219,
GSE31210,
GSE37745
GSE50081.
study
focused
on
33
genes
regulated
or
(mRG),
which
were
to
form
mRGs
clusters
mRG
differentially
expressed
(mRG‐DEG
clusters).
Our
subsequent
LASSO
regression
analysis
trained
m6A/m5C/m1A‐related
lncRNA
(mRLncSig)
using
lncRNAs
exhibited
differential
expression
among
mRG‐DEG
had
prognostic
value.
model's
accuracy
underwent
via
Kaplan–Meier
analysis,
Cox
regression,
ROC
tAUC
evaluation,
PCA
examination
nomogram
predictor
validation.
In
evaluating
immunotherapeutic
potential
signature,
we
employed
multiple
bioinformatics
algorithms
concepts
through
various
analyses.
These
included
seven
newly
developed
immunoinformatic
algorithms,
well
evaluations
TMB,
TIDE
immune
checkpoints.
Additionally,
identified
validated
promising
agents
target
high‐risk
mRLncSig
To
validate
real‐world
pattern
mRLncSig,
real‐time
PCR
carried
out
human
LUAD
tissues.
signature's
ability
perform
pan‐cancer
settings
also
evaluated.
a
10‐lncRNA
have
power
cohort.
Real‐time
applied
verify
actual
manifestation
each
gene
real
world.
immunotherapy
revealed
an
association
status.
found
be
closely
linked
several
checkpoints,
such
IL10,
IL2,
CD40LG,
SELP,
BTLA
CD28,
could
appropriate
targets
Among
patients,
our
12
candidate
drugs
verified
gemcitabine
most
significant
one
effective
treating
discovered
some
play
crucial
role
certain
cancer
types,
thus,
may
require
further
attention
future
studies.
According
findings
this
study,
use
has
aid
forecasting
serve
immunotherapy.
Moreover,
assist
identifying
therapeutic
more
effectively.
Language: Английский
RNA modifications in long non-coding RNAs and their implications in cancer biology
Bioorganic & Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
113, P. 117922 - 117922
Published: Sept. 13, 2024
Language: Английский
YTHDC1 phase separation drives the nuclear export of m6A-modified lncNONMMUT062668.2 through the transport complex SRSF3–ALYREF–XPO5 to aggravate pulmonary fibrosis
Sony Su Chen,
No information about this author
Yujie Wang,
No information about this author
Jinjin Zhang
No information about this author
et al.
Cell Death and Disease,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: April 12, 2025
Fibroblast-to-myofibroblast
differentiation
is
the
main
cytopathologic
characteristic
of
pulmonary
fibrosis.
However,
its
underlying
molecular
mechanism
remains
poorly
understood.
This
study
elucidated
that
nuclear
export
lncNONMMUT062668.2
(lnc668)
exacerbated
fibrosis
by
activating
fibroblast-to-myofibroblast
differentiation.
Mechanistic
research
revealed
histone
H3K9
lactylation
in
promoter
region
N6-methyladenosine
(m6A)
writer
METTL3
was
enriched
to
enhance
transcription,
leading
lnc668
m6A
modification.
Meanwhile,
reader
YTHDC1
recognized
m6A-modified
and
elevated
METTL3-mediated
Subsequently,
phase-separating
promoted
lnc668.
In
this
process,
formed
a
pore
complex
with
serine/arginine-rich
splicing
factor
3,
Aly/REF
factor,
exportin-5
assist
translocation
from
nucleus
cytoplasm.
After
export,
facilitated
translation
stability
host
gene
phosphatidylinositol-binding
clathrin
assembly
protein
activate
differentiation,
aggravation
fibrosis,
which
also
depended
on
phase
separation.
first
clarified
separation
crucial
for
modification,
profibrotic
role
exacerbating
These
findings
provide
new
insights
into
cytoplasmic
lncRNAs
identified
potential
targets
therapy.
Language: Английский
G0 arrest gene patterns to predict the prognosis and drug sensitivity of patients with lung adenocarcinoma
Yong Ma,
No information about this author
Zhilong Li,
No information about this author
Dongbing Li
No information about this author
et al.
PLoS ONE,
Journal Year:
2024,
Volume and Issue:
19(8), P. e0309076 - e0309076
Published: Aug. 19, 2024
G0
arrest
(G0A)
is
widely
recognized
as
a
crucial
factor
contributing
to
tumor
relapse.
The
role
of
genes
related
G0A
in
lung
adenocarcinoma
(LUAD)
was
unclear.
This
study
aimed
develop
gene
signature
based
on
for
LUAD
patients
and
investigate
its
relationship
with
prognosis,
immune
microenvironment,
therapeutic
response
LUAD.
We
use
the
TCGA-LUAD
database
discovery
cohort,
focusing
specifically
associated
pathway.
used
various
statistical
methods,
including
Cox
lasso
regression,
model.
validated
model
using
bulk
transcriptome
single-cell
datasets
(GSE50081,
GSE72094,
GSE127465,
GSE131907
EMTAB6149).
GSEA
enrichment
CIBERSORT
algorithm
gain
insight
into
annotation
signaling
pathway
characterization
microenvironment.
evaluated
immunotherapy,
chemotherapy,
targeted
therapy
these
patients.
expression
six
cell
lines
by
quantitative
real-time
PCR
(qRT-PCR).
Our
successfully
established
six-gene
(CHCHD4,
DUT,
LARP1,
PTTG1IP,
RBM14,
WBP11)
that
demonstrated
significant
predictive
power
overall
survival
It
independent
prognostic
value
To
enhance
clinical
applicability,
we
developed
nomogram
this
signature,
which
showed
high
reliability
predicting
patient
outcomes.
Furthermore,
observed
association
between
G0A-related
risk
microenvironment
well
drug
susceptibility,
highlighting
potential
guide
personalized
treatment
strategies.
were
significantly
upregulated
lines.
holds
contribute
improved
prediction
new
therapies
Language: Английский
Establishment of potential lncRNA-related hub genes involved competitive endogenous RNA in lung adenocarcinoma
Yong Li,
No information about this author
Danfei Shi,
No information about this author
Yan Jiang
No information about this author
et al.
BMC Cancer,
Journal Year:
2024,
Volume and Issue:
24(1)
Published: Nov. 9, 2024
Long
non-coding
RNAs
(lncRNAs)
have
a
notable
role
in
the
diagnosis
and
prognosis
of
cancer.
However,
associations
between
lncRNA-related
hub
genes
(LRHGs)
expression
corresponding
outcomes
not
been
fully
understood
lung
adenocarcinoma
(LUAD).
Here,
total
71
patients
diagnosed
with
LUAD
60
healthy
volunteers
at
The
First
Affiliated
Hospital
Huzhou
University
from
April,
2023
to
December,
were
enrolled
present
study.
A
LRHGs
model
was
established
using
least
absolute
shrinkage
selection
operator
analyses
Cancer
Genome
Atlas-LUAD
datasets.
underlying
mechanisms
investigated
via
Gene
Set
Enrichment
Analysis
Variation
Analysis.
Additionally,
diagnostic
serum
HOXD
cluster
antisense
RNA
2
(HOXD-AS2)
assessed
by
receiver
operating
characteristic
(ROC)
curve
analysis.
Lastly,
TCGA-LUAD
samples
divided
into
high-
low-HOXD-AS2
groups
based
on
median
expression.
HOXD-AS2
miR-4538
as
well
Calmodulin-Dependent
Protein
Kinase
Type
II
subunit
Beta
(CAMK2B)
levels
conducted
through
Pearson
correlation
comprehensive
analysis
identified
141
differentially
expressed
lncRNAs
539
tissues
59
normal
samples.
prognostic
marker
for
overall
survival
constructing
predictive
signature
consisting
9
LRHGs.
Subsequently,
474
categorized
high
or
low-risk
group
risk
score.
An
independent
constructed
confirm
validity
this
categorization.
Further
comparisons
clinicopathological
features
LRHG-related
pathways
performed
two
groups.
Examinations
LRHG
clusters
association
immune
infiltration
also
conducted.
shown
be
elevated
compared
matched
tissues,
level
notably
increased
controls.
results
ROC
indicated
that
sensitivity
specificity
higher
than
cytokeratin-19
fragment
(CYFRA21-1),
which
is
LUAD.
negatively
associated
expression,
but
CAMK2B
showed
positive
study
therefore
model,
particularly
HOXD-AS2,
could
independently
diagnose
predict
LUAD,
suggested
mechanism
HOXD-AS2/miR-4538/CAMK2B,
might
offer
efficient
strategies
treatment.
Language: Английский