Multi-omics landscape of alternative splicing in diffuse midline glioma reveals immune- and neural-driven subtypes with implications for spliceosome-targeted therapy
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 16, 2025
Introduction
H3K27-altered
diffuse
midline
glioma
(DMG)
is
a
highly
aggressive
subtype,
accounting
for
approximately
60%
of
pediatric
high-grade
gliomas,
with
median
survival
less
than
12
months.
Due
to
its
predominant
localization
in
the
brainstem,
conventional
surgical
resection
often
unfeasible,
underscoring
urgent
need
alternative
therapeutic
strategies.
While
previous
studies
on
DMG
have
primarily
focused
regulatory
mechanisms
at
protein
level,
role
splicing
remains
largely
unexplored.
Given
potential
impact
gene
regulation
and
tumor
progression,
comprehensive
analysis
could
provide
novel
insights
into
targeted
or
immune
strategies,
complementing
existing
transcriptomic
DMG.
Methods
To
investigate
landscape
DMG,
we
performed
transcriptome
sequencing
(RNA-seq)
patient-derived
H3WT
cell
lines,
integrating
these
data
RNA-seq
single-cell
(scRNA-seq)
datasets
from
published
sources.
This
approach
enabled
us
delineate
validate
distinct
features
cellular
level.
Results
Our
multi-omics
revealed
significant
transcriptional
alterations
compared
particularly
pathways
related
neuro-regulation,
metabolism,
immunity.
Further
in-depth
identified
extensive
changes
predominantly
associated
RNA
modifications
key
extracellular
matrix
nucleotide
metabolism.
Integrating
findings,
characterized
five
RNA-associated
proteins
that
binary
classification
neural
subtypes,
each
subtype
exhibiting
prognostic
features.
Notably,
RALYL
as
regulator
progression.
Discussion
findings
indicate
exhibits
alterations,
which
play
crucial
roles
tumorigenesis
Additionally,
our
study
an
RNA-binding
protein-based
factor,
highlighting
target.
Язык: Английский
Long Non-Coding TP73-AS1: A Potential Biomarker and Therapeutic Target in Cancer
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(8), С. 3886 - 3886
Опубликована: Апрель 20, 2025
Tumor
protein
73
antisense
RNA
1
(TP73-AS1),
a
newly
discovered
long
non-coding
(lncRNA),
the
dysregulated
expression
of
which
is
closely
related
to
occurrence,
drug
resistance,
and
prognosis
various
cancers.
Exploring
regulatory
mechanism
TP73-AS1
provides
new
research
direction
for
cancer
diagnosis
treatment.
On
this
basis,
we
briefly
review
molecular
structural
dual
roles
in
cancer.
In
addition,
outline
its
three
mechanisms
cancer:
binding
proteins,
regulating
signaling
pathways,
serving
as
sponges.
Subsequently,
introduce
role
common
malignant
tumors
such
gastric
(GC),
lung
cancer,
colorectal
(CRC),
etc.
Last,
emphasis
given
potential
clinical
value
TP73-AS1,
especially
single
nucleotide
polymorphisms
lncRNA
are
associated
with
risk
GC
CRC.
Therefore,
highlights
significance
novel
biomarker
therapeutic
target.
Язык: Английский