Aging
is
a
universal
physiological
phenomenon,
and
chronic
age-related
diseases
have
become
one
of
the
leading
causes
human
mortality,
accounting
for
nearly
half
all
deaths.
Studies
shown
that
reducing
incidence
these
can
not
only
extend
lifespan
but
also
promote
healthy
aging.
In
recent
years,
potential
role
non-histone
high-mobility
group
proteins
(HMGs)
in
regulation
aging
has
attracted
widespread
attention.
HMGs
play
critical
roles
cellular
senescence
associated
through
various
pathways,
encompassing
multi-layered
mechanisms
involving
protein
interactions,
molecular
regulation,
chromatin
dynamics.
This
review
provides
comprehensive
analysis
interactions
between
HMG
family
senescence-associated
secretory
phenotype
(SASP),
structure,
histone
modifications,
offering
deeper
exploration
pivotal
functions
impacts
process.
Furthermore,
we
summarize
findings
on
contributions
to
diseases.
regulate
inflammation
modulating
SASP
influence
genomic
stability
cell
fate
decisions
via
with
histones.
Targeting
holds
great
delaying
progression
its
aims
provide
systematic
overview
proteins’
lay
solid
foundation
future
anti-aging
drug
development
therapeutic
strategies.
With
advancing
understanding
by
which
aging,
developing
interventions
targeting
may
emerge
as
promising
approach
extending
enhancing
healthspan.
Frontiers in Oncology,
Год журнала:
2024,
Номер
14
Опубликована: Март 1, 2024
High
mobility
group
protein
1
(HMGB1)
plays
a
complex
role
in
tumor
biology.
When
released
into
the
extracellular
space,
it
binds
to
receptor
for
advanced
glycation
end
products
(RAGE)
located
on
cell
membrane,
playing
an
important
development
by
regulating
number
of
biological
processes
and
signal
pathways.
In
this
review,
we
outline
multifaceted
functions
HMGB1/RAGE
axis,
which
encompasses
proliferation,
apoptosis,
autophagy,
metastasis,
angiogenesis.
This
axis
is
instrumental
progression,
promoting
angiogenesis
while
inhibiting
through
pivotal
signaling
pathways,
including
MAPK,
NF-κB,
PI3K/AKT,
ERK,
STAT3.
Notably,
small
molecules,
such
as
miRNA-218,
ethyl
pyruvate
(EP),
glycyrrhizin
exhibit
ability
inhibit
restraining
development.
Therefore,
deeper
understanding
mechanisms
tumors
great
importance,
inhibitors
targeting
warrants
further
exploration.
Cancer Communications,
Год журнала:
2024,
Номер
44(9), С. 1018 - 1041
Опубликована: Июль 19, 2024
Abstract
Background
N4‐acetylcytidine
(ac4C)
represents
a
novel
messenger
RNA
(mRNA)
modification,
and
its
associated
acetyltransferase
N‐acetyltransferase
10
(NAT10)
plays
crucial
role
in
the
initiation
progression
of
tumors
by
regulating
mRNA
functionality.
However,
hepatocellular
carcinoma
(HCC)
development
prognosis
is
largely
unknown.
This
study
aimed
to
elucidate
NAT10‐mediated
ac4C
HCC
provide
promising
therapeutic
approach.
Methods
The
levels
were
evaluated
dot
blot
ultra‐performance
liquid
chromatography‐tandem
mass
spectrometry
with
harvested
tissues.
expression
NAT10
was
investigated
using
quantitative
real‐time
polymerase
chain
reaction,
western
blotting,
immunohistochemical
staining
across
91
cohorts
patients.
To
explore
underlying
mechanisms
NAT10‐ac4C
HCC,
we
employed
comprehensive
approach
integrating
acetylated
immunoprecipitation
sequencing,
sequencing
ribosome
profiling
analyses,
along
immunoprecipitation,
pull‐down,
spectrometry,
site‐specific
mutation
analyses.
drug
affinity
responsive
targets
stability,
cellular
thermal
shift
assay,
surface
plasmon
resonance
assays
performed
assess
specific
binding
Panobinostat.
Furthermore,
efficacy
targeting
for
treatment
elucidated
through
vitro
experiments
cells
vivo
mouse
models.
Results
Our
investigation
revealed
significant
increase
both
level
HCC.
Notably,
elevated
poor
outcomes
Functionally,
silencing
suppressed
proliferation
metastasis
vivo.
Mechanistically,
stimulates
modification
within
coding
sequence
(CDS)
high
mobility
group
protein
B2
(HMGB2),
which
subsequently
enhances
HMGB2
translation
facilitating
eukaryotic
elongation
factor
2
(eEF2)
sites
on
mRNA's
CDS.
Additionally,
high‐throughput
compound
library
screening
Panobinostat
as
potent
inhibitor
modification.
inhibition
significantly
attenuated
growth
Conclusions
identified
oncogenic
epi‐transcriptome
axis
involving
NAT10‐ac4C/eEF2‐HMGB2,
pivotal
metastasis.
validates
potential
this
treatment.
Proceedings of the National Academy of Sciences,
Год журнала:
2025,
Номер
122(5)
Опубликована: Янв. 27, 2025
Recent
studies
have
demonstrated
that
chronic
stress
can
enhance
the
development
of
multiple
human
diseases,
including
cancer.
However,
role
in
esophageal
carcinogenesis
and
its
underlying
molecular
mechanisms
remain
unclear.
This
study
uncovered
dysregulated
cholesterol
metabolism
significantly
promotes
under
conditions.
Our
findings
indicate
persistent
elevation
glucocorticoids
induced
by
stimulates
uptake,
contributing
to
carcinogenesis.
The
activated
glucocorticoid
receptor
(GCR)
enrichment
at
promoter
region
High
Mobility
Group
Box
2
(HMGB2)
facilitates
transcription.
As
a
transcription
coactivator,
HMGB2
enhances
Sterol
Regulatory
Element
Binding
Transcription
Factor
1
(SREBF1)
regulates
through
LDL
particle
uptake
into
cells
via
Low
Density
Lipoprotein
Receptor
(LDLR).
These
results
emphasize
significant
impact
on
establish
disorder
as
crucial
link
between
ESCC.
implications
suggest
effectively
managing
may
serve
viable
strategy
for
preventing
treating
ABSTRACT
Senescence
is
a
cell
fate
associated
with
age‐related
pathologies;
however,
senescence
markers
are
not
well‐defined.
Using
single
multi‐isotope
imaging
mass
spectrometry
(MIMS),
we
identified
hypercondensed,
transcriptionally
silent
DNA
globules
in
model
induced
by
dysfunctional
telomeres.
This
architectural
phenomenon
was
geographically
clustered
transcriptional
repression
across
somatic
chromosomes
over‐representation
of
cycle
genes.
Senescence‐stimuli
higher
frequency
cells
that
exhibited
concentrated
relative
to
control
cells.
also
observed
multiple
other
models,
including
replicative
and
irradiation.
We
further
an
enrichment
common
pathways
all
models
senescence,
suggesting
cellular
response
this
silencing
phenomenon.
Such
large‐scale
chromosomal
segments
rather
than
individual
genes
may
explain
heterogeneity
putative
trajectory
toward
deep,
irreversible
senescence.
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
165, С. 115118 - 115118
Опубликована: Июль 10, 2023
Cardiovascular
disease
(CVD)
is
the
most
fatal
that
causes
sudden
death,
and
inflammation
contributes
substantially
to
its
occurrence
progression.
The
prevalence
of
CVD
increases
as
population
ages,
pathophysiology
complex.
Anti-inflammatory
immunological
modulation
are
potential
methods
for
prevention
treatment.
High-Mobility
Group
(HMG)
chromosomal
proteins
one
abundant
nuclear
nonhistone
which
act
inflammatory
mediators
in
DNA
replication,
transcription,
repair
by
producing
cytokines
serving
damage-associated
molecular
patterns
responses.
common
well-studied
HMG
those
with
an
HMGB
domain,
participate
a
variety
biological
processes.
HMGB1
HMGB2
were
first
members
family
be
identified
present
all
investigated
eukaryotes.
Our
review
primarily
concerned
involvement
CVD.
purpose
this
provide
theoretical
framework
diagnosing
treating
discussing
structure
function
HMGB2.
Cancer
is
a
significant
global
health
problem
characterized
by
increased
incidence
and
large
disparities
in
outcomes.
There
compelling
need
to
identify
novel
biomarkers
enhance
early
detection,
prognosis,
tailored
therapies.
Growth
arrest-specific
transcript
5
(GAS5)
long
noncoding
RNA
(lncRNA)
with
potential
as
tumor
suppressor
subset
of
cancers.
Its
roles
the
diagnosis,
therapy
across
cancer
types
remain
underexplored.
In
this
study,
pan-cancer
comprehensive
analysis
expression
status
GAS5
was
conducted
using
various
bioinformatics
tools
genomic
datasets,
including
Tumor
Immune
Estimation
Resource
(TIMER),
Gene
Expression
Profiling
Interactive
Analysis
(GEPIA),
University
Alabama
at
Birmingham
Data
Portal
(UALCAN),
Omnibus
(GEO).
The
different
cancers
determined
then
evaluated
for
its
correlation
clinicopathological
parameters,
immune
cell
infiltration,
survival
outcome,
methylation
promoter.
Additionally,
Kaplan-Meier
plotter
(KMP)
used
overall
assessment,
cBioPortal
tool
applied
genetic
alteration
radiation
response
assessment.
Functional
analyses
were
performed
data
from
Long
Noncoding
Arrays
(lnCAR)
database,
which
included
coexpression
networks,
competing
endogenous
(ceRNA)
interactions,
pathway
enrichment.
Our
analysis,
based
on
three
showed
that
significantly
upregulated
mainly
cholangiocarcinoma
(CHOL),
kidney
renal
clear
carcinoma
(KIRC),
liver
hepatocellular
(LIHC)
(p
<
0.05).
On
contrary,
it
downregulated
breast
invasive
(BRCA),
chromophobe
(KICH),
uterine
corpus
endometrial
(UCEC).
High
associated
poor
LIHC
KIRC
Promoter
hypomethylation
identified
key
regulatory
mechanism
CHOL,
KIRC,
exhibited
positive
correlations
infiltration
(e.g.,
CD4+
T
cells,
CD8+
macrophages)
negative
B
dendritic
cells)
KIRC.
network
has
established
ceRNA
interacts
36
miRNAs
95
protein-coding
genes,
affecting
pathways
like
metabolism,
mitogen-activated
protein
kinase
(MAPK)
signaling,
cytokine-cytokine
receptor
interactions
alterations
may
have
an
impact
levels
how
functions
during
treatment.
Furthermore,
epigenetic
control
DNA
suggests
possible
targets
personalized
treatment
methods.
This
offers
foundation
diagnostic
prognostic
biomarker,
especially
prominent
LIHC,
additional
relevance
Identification
tissue-specific
mechanisms
cells
opens
new
perspectives
into
context-dependent
functionality
GAS5.
These
findings
highlight
developing
targeted
therapies
advancing
medicine,
paving
way
future
research
GAS5-based
strategies
cancer.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Март 31, 2025
High
mobility
group
box
2
(HMGB2),
one
of
the
HMGB
domain
proteins,
may
play
a
significant
role
in
cancer
development
and
progression.
Recent
scientific
investigations
have
hinted
at
potential
clinical
relevance
HMGB2,
particularly
patients
where
its
expression
levels
been
observed
to
be
elevated.
However,
precise
impact
HMGB2
on
prognosis
tumors
remains
an
area
ongoing
research.
To
best
our
understanding,
study
represents
meta-analysis
that
elucidates
connection
between
outcomes
diverse
types.
We
executed
thorough
systematic
search
literature
across
PubMed,
Web
Science,
Embase,
CNKI,
Wanfang
databases.
Following
this,
we
conducted
quantitative
using
statistical
tools
such
as
StataMP16
RevMan5.3.
The
primary
focus
analysis
was
assess
relationship
overall
survival
(OS),
disease-free
(DFS),
well
various
clinicopathological
characteristics
by
calculating
hazard
ratio
(HR).
Additionally,
validated
findings
examining
patterns
different
types
Gene
Expression
Profiling
Interactive
Analysis
(GEPIA)
online
platform.
Our
incorporated
data
from
17
studies,
encompassing
total
2555
patients.
results
revealed
statistically
association
high
shorter
OS
(HR,
1.40
;95%
CI:
1.10-1.70;
P
<
0.001),
especially
digestive
(
HR,
2.09
(95%
1.54-2.63;
I2
=
0.0%,P
0.424).
Furthermore,
GEPIA
demonstrated
consistent
upregulation
most
types,
with
downregulation
LAML.
underscore
detrimental
correlation
cancers.
This
discovery
could
pave
way
for
innovative
prognostic
biomarkers
therapeutic
targets
specifically
target
offering
new
avenues
management
treatment
