Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Июль 19, 2023
Abstract
Introduction:
Papillary
thyroid
carcinomas
(PTC)
are
the
most
common
malignancies
that
often
diagnosed
as
microcarcinomas
when
tumour
is
less
than
one
centimetre
in
diameter.
Currently,
there
no
valid
stratification
strategies
would
reliably
assess
risk
of
lateral
neck
metastases
and
optimize
surgical
treatment.
Materials
methods:
Aiming
to
find
potential
tissue
biomarkers
metastatic
potential,
we
conducted
a
cross-sectional
proteomic
study
on
formalin-fixed
paraffin-embedded
tissues
(N
=
10)
non-metastatic
papillary
microcarcinoma
patients.
Samples
were
analysed
individually
using
liquid-chromatography
/
mass
spectrometry,
differentially
expressed
proteins
(DEP)
functionally
annotated.
Results:
We
identified
five
overexpressed
DEPs
group
(EPB41L2,
CSE1L,
GLIPR2,
FGA
FGG)
with
known
association
biology.
Using
bioinformatics
tools,
found
markedly
different
profiles
significantly
enriched
biological
processes
between
two
groups.
Conclusion:
The
might
have
role
for
PTC
metastases.
However,
further
prospective
research
needed
order
confirm
our
findings.
Abstract
Acetaminophen
(APAP)
overdose
is
a
major
cause
of
drug‐induced
liver
injury.
Sirtuins
5
(SIRT5)
has
been
implicated
in
the
development
various
diseases.
However,
its
involvement
APAP‐induced
acute
injury
(AILI)
remains
unclear.
The
present
study
aimed
to
explore
role
SIRT5
AILI.
expression
dramatically
downregulated
by
APAP
administration
mouse
livers
and
AML12
hepatocytes.
deficiency
not
only
exacerbates
inflammatory
response,
but
also
worsens
mitochondrial
oxidative
stress.
Conversely,
opposite
pathological
biochemical
changes
are
observed
mice
with
overexpression.
Mechanistically,
quantitative
succinylome
analysis
site
mutation
experiments
revealed
that
desuccinylated
aldehyde
dehydrogenase
2
(ALDH2)
at
lysine
385
maintained
enzymatic
activity
ALDH2,
resulting
suppression
inflammation
Furthermore,
succinylation
ALDH2
abolished
protective
effect
against
AILI,
AILI
dependent
on
desuccinylation
K385.
Finally,
virtual
screening
natural
compounds
Puerarin
promoted
desuccinylase
further
attenuated
Collectively,
showed
SIRT5‐ALDH2
axis
plays
critical
progression
might
be
strategy
for
therapeutic
intervention.
Abstract
Objective
This
study
was
designed
to
investigate
the
regulatory
effects
of
kinesin
family
member
(KIF)
23
on
anaplastic
thyroid
cancer
(ATC)
cell
viability
and
migration
underlying
mechanism.
Methods
Reverse
transcription-quantitative
polymerase
chain
reaction
(RT-qPCR)
used
analyze
levels
KIF23
in
ATC
cells.
Besides,
sirtuin
(SIRT)
7
cells
were
detected
using
counting
kit-8,
transwell
wound
healing
assays.
The
interaction
between
SIRT7
evaluated
by
co-immunoprecipitation
(Co-IP)
assay.
succinylation
(succ)
analyzed
western
blot.
Results
expression
upregulated
Silencing
suppressed
8505C
BCPAP
KIF23-succ
level
decreased
interacted
with
inhibit
at
K537
site
human
embryonic
kidney
(HEK)-293T
Overexpression
enhanced
protein
stability
HEK-293T
overexpression
promoted
cells,
which
partly
blocked
silenced
SIRT7.
Conclusions
proliferation
regulating
desuccinylation
KIF23.
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
168, С. 115713 - 115713
Опубликована: Окт. 16, 2023
Metabolic
reprogramming
is
a
common
hallmark
of
cancers
and
involves
alterations
in
many
metabolic
pathways
during
tumor
initiation
progression.
However,
the
cancer-specific
modulation
requires
further
elucidation.
Succinylation,
newly
identified
protein
posttranslational
modification
(PTM),
participates
cellular
processes
by
transferring
succinyl
group
to
residue
target
protein,
which
related
various
pathological
disorders
including
cancers.
In
recent
years,
there
has
been
gradual
increase
number
studies
on
regulation
tumors
succinylation.
Notably,
accumulating
evidence
suggests
that
succinylation
can
mediate
cancer
cell
metabolism
altering
structure
or
activity
metabolism-related
proteins
plays
vital
roles
reprogramming.
Furthermore,
some
antitumor
drugs
have
linked
succinylation-mediated
tumor-associated
metabolism.
To
better
elucidate
lysine
mediated
reprogramming,
this
review
mainly
summarizes
effects
tumors,
focusing
tumorigenesis
development,
will
provide
new
directions
for
diagnosis
as
well
possible
therapeutic
targets.
Pharmaceuticals,
Год журнала:
2023,
Номер
16(4), С. 559 - 559
Опубликована: Апрель 7, 2023
Although
biologically
targeted
therapies
based
on
key
oncogenic
mutations
have
made
significant
progress
in
the
treatment
of
locally
advanced
or
metastatic
thyroid
cancer,
challenges
drug
resistance
are
urging
us
to
explore
other
potentially
effective
targets.
Herein,
epigenetic
modifications
including
DNA
methylation,
histone
modifications,
non-coding
RNAs,
chromatin
remodeling
and
RNA
alterations,
reviewed
therapeutic
agents
for
such
as
DNMT
(DNA
methyltransferase)
inhibitors,
HDAC
(histone
deacetylase)
BRD4
(bromodomain-containing
protein
4)
KDM1A
(lysine
demethylase
1A)
inhibitors
EZH2
(enhancer
zeste
homolog
2)
updated.
We
conclude
that
epigenetics
is
promising
a
target
cancer
further
clinical
trials
warranted.
Translational Oncology,
Год журнала:
2023,
Номер
33, С. 101673 - 101673
Опубликована: Апрель 14, 2023
Non-Small
Cell
Lung
Cancer
(NSCLC)
is
the
most
prevalent
kind
of
lung
cancer
with
around
85%
total
cases.
Despite
vast
therapies
being
available,
survival
rate
low
(5
year
15%)
making
it
essential
to
comprehend
mechanism
for
NSCLC
cell
and
progression.
The
plethora
evidences
suggests
that
Post
Translational
Modification
(PTM)
such
as
phosphorylation,
methylation,
acetylation,
glycosylation,
ubiquitination
SUMOylation
are
involved
in
various
types
progression
metastasis
including
NSCLC.
Indeed,
an
in-depth
understanding
PTM
associated
biology
will
provide
novel
therapeutic
targets
insight
into
current
sophisticated
paradigm.
Herein,
we
reviewed
key
PTMs,
epigenetic
modulation,
PTMs
crosstalk
along
proteogenomics
analyze
also,
highlighted
how
epi‑miRNA,
miRNA
inhibitors
modulators
serve
promising
therapeutics.
The
microbial
flora
has
always
been
a
center
of
interest
for
the
identification
novel
bioactive
secondary
metabolites
(SMs)
used
against
diversity
infections
and
ailments.
These
compounds
are
produced
by
hosts
in
response
to
different
stress
conditions.
Novobiocin
naturally
synthesized
Streptomyces
spheroids,
Echinocandin
B
from
Emericella
rugulosa,
Penicillin
Penicillium
chrysogenum,
Gentamycin
Micromonospora
purpurea
such
examples.
In
nature,
genes,
either
cryptic
or
compounds,
synthesize
trace
amounts
under
specific
environmental
conditions,
physiological
conditions
which
make
their
bioavailability
scarcer.
Different
strategies
as
induced
stimuli,
cloning
genes
control
strong
promoters,
downregulating
expression
negative
regulators,
epigenetic
manipulations,
etc.
have
tried
increase
SM
bioavailability.
posttranslational
modifications
histones
proteins
render
regulate
also
implied.
Here,
this
chapter,
we
emphasized
regulation
enhancement
production
therapeutically
significant
fungi.
DNA
wrapped
around
undergo
that
facilitate
chromatin
packaging
loose
(euchromatin)
tight
(heterochromatin).
Such
alterations
epigenetically
modulate
responsible
regulating
metabolic
events.
Relevance
approaches
use
Histone
deacetylase
inhibitors
(HDACs)
methyl
transferase
(DNMTs)
concern
fungal
compounds.
could
be
intrinsically
programmed
affected
externally.
studies
provided
supportive
arguments
about
modifiers
increasing
act
locally
globally
inducing
repressing
synthesis
genes.
earlier
studied
modulation
metabolite
For
instance,
5-azacytidine,
hydralazine
hydrochloride,
trichostatin
A,
trapoxin
B,
chapter
elaborates
on
more
developed
understanding
histone
activation/induction
yield
pharmacologically
fungal-derived
Journal of Cell Communication and Signaling,
Год журнала:
2024,
Номер
18(2)
Опубликована: Апрель 12, 2024
Abstract
lncRNA
ZFAS1
was
identified
to
facilitate
thyroid
cancer,
but
its
role
in
medullary
carcinoma
(MTC)
remains
unknown.
This
study
aimed
unravel
the
potential
function
of
this
MTC
by
investigating
involvement
a
ceRNA
network
that
regulates
invasion.
Proliferation,
invasion,
and
migration
cells
were
evaluated
using
EdU
staining
Transwell
assays.
Immunoprecipitation
(IP)
assays,
dual‐fluorescence
reporter,
RNA
IP
assays
employed
examine
binding
interaction
among
genes.
Nude
mice
used
explore
vivo.
EPAS1
upregulated
MTC.
Silencing
inhibited
cell
proliferation
invasion
under
hypoxic
conditions,
which
reduced
protein
levels.
UCHL1
knockdown
increased
ubiquitination.
positively
regulated
expression
miR‐214‐3p.
Finally,
silencing
significantly
repressed
tumor
formation
metastasis
LncRNA
promotes
upregulating
via
miR‐214‐3p/UCHL1
axis.
Heliyon,
Год журнала:
2024,
Номер
10(13), С. e34032 - e34032
Опубликована: Июль 1, 2024
Thyroid
cancer
is
the
most
common
malignant
tumor
of
endocrine
system,
and
evidence
suggests
that
post-translational
modifications
(PTMs)
epigenetic
alterations
play
an
important
role
in
its
development.
Recently,
there
has
been
increasing
linking
dysregulation
ubiquitinating
enzymes
deubiquitinases
with
thyroid
cancer.
This
review
aims
to
summarize
our
current
understanding
ubiquitination-modifying
cancer,
including
their
regulation
oncogenic
pathways
proteins.
The
development
progression
requires
further
study,
which
will
provide
new
insights
into
prevention,
treatment
novel
agents.