Clinical and Translational Medicine,
Год журнала:
2024,
Номер
14(1)
Опубликована: Янв. 1, 2024
Abstract
Background
Prostate
cancer
(PCa)
initially
shows
satisfactory
response
to
therapies
targeting
the
androgen
receptor
(AR).
However,
progression
a
castration‐resistant
stage
indicates
poor
prognosis
in
PCa
patients.
AR
signalling
still
plays
central
role
most
prostate
cancers
(CRPC).
Therefore,
unveiling
mechanisms
of
reactivation
under
androgen‐deprived
conditions
is
imperative
discover
novel
therapeutic
targets
for
CRPC.
Methods
Using
an
integrative
analysis
transcriptomics
three
independent
cohorts
and
published
landscape
AR‐regulated
long
non‐coding
RNA
(lncRNA),
lncRNA
LINC01126
was
selected
as
candidate
gene
that
could
drive
CRPC
further
study.
Quantitative
reverse
transcription
polymerase
chain
reaction,
situ
hybridisation
(ISH)
fluorescent
ISH
were
performed
detect
tissues
cells.
The
functional
mechanism
investigated
using
vitro
vivo
gain
loss
function
assays.
Results
LINC01126,
identified
AR‐repressed
lncRNA,
significantly
upregulated
after
AR‐targeted
therapies.
In
addition,
we
found
associated
with
prognosis.
We
also
proved
stabilised
protein
enhanced
nuclear
translocation
transactivation
by
promoting
transition
from
O‐GlcNAcylation
at
threonine
80
phosphorylation
serine
81
(S81)
within
protein.
Mechanism
revealed
facilitates
interaction
CDK9
impedes
binding
O‐linked
N‐acetylglucosamine
(O‐GlcNAc)
transferase
AR.
Consequently,
expression
sufficient
activate
without
androgen.
overexpression
increased,
whereas
knockdown
decreased
castration
resistance
traits
cells
vivo.
Furthermore,
our
data
showed
LINC01126‐targeting
antisense
oligonucleotides
(ASO)
substantially
inhibited
vitro.
Conclusions
Our
research
expands
functions
sustaining
androgen‐independent
activity
reveals
may
be
new
target
PCa.
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
158, С. 114168 - 114168
Опубликована: Янв. 3, 2023
The
categorization
of
cancers
demonstrates
that
prostate
cancer
is
the
most
common
malignancy
in
men
and
it
causes
high
death
annually.
Prostate
patients
are
diagnosed
mainly
via
biomarkers
such
as
PSA
test
show
poor
prognosis.
cells
rapidly
diffuse
into
different
parts
body
their
metastasis
also
a
reason
for
death.
Current
therapies
include
chemotherapy,
surgery
radiotherapy
well
targeted
therapy.
progression
regulated
by
factors
STAT3
signaling
among
them.
Growth
cytokines
IL-6
can
induce
shows
carcinogenic
impact.
Activation
occurs
promotes
malignant
behavior
tumor
cells.
Induction
increases
glycolysis
proliferation
prevents
apoptosis.
Furthermore,
induces
EMT
mechanism
increasing
metastasis.
stimulates
drug
resistance
limitation
current
works
lack
experiment
related
to
role
radio-resistance
tumor.
Calcitriol,
capsazepine
β-elemonic
compounds
capable
targeting
its
inhibition
In
addition
natural
products,
small
molecules
have
been
developed
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(9), С. 7130 - 7145
Опубликована: Апрель 17, 2024
Multitarget
medications
represent
an
appealing
therapy
against
the
disease
with
multifactorial
abnormalities─cancer.
Therefore,
simultaneously
targeting
son
of
sevenless
1
(SOS1)
and
epidermal
growth
factor
receptor
(EGFR),
two
aberrantly
expressed
proteins
crucial
for
oncogenesis
progression
prostate
cancer,
may
achieve
active
antitumor
effects.
Here,
we
discovered
dual
SOS1/EGFR-targeting
compounds
via
pharmacophore-based
docking
screening.
The
most
prominent
compound
SE-9
exhibited
nanomolar
inhibition
activity
both
SOS1
EGFR
efficiently
suppressed
phosphorylation
ERK
AKT
in
cancer
cells
PC-3.
Cellular
assays
also
revealed
that
displayed
strong
antiproliferative
activities
through
diverse
mechanisms,
such
as
induction
cell
apoptosis
G1
phase
cycle
arrest,
well
reduction
angiogenesis
migration.
Further
vivo
findings
showed
potently
inhibited
tumor
PC-3
xenografts
without
obvious
toxicity.
Overall,
is
a
novel
dual-targeting
SOS1/EGFR
inhibitor
represents
promising
treatment
strategy
cancer.
Non-coding RNA Research,
Год журнала:
2024,
Номер
9(2), С. 388 - 406
Опубликована: Фев. 1, 2024
Long
noncoding
RNAs
(lncRNAs)
are
RNA
transcripts
longer
than
200
nucleotides
that
do
not
code
for
proteins
but
have
been
linked
to
cancer
development
and
metastasis.
Metastasis-associated
lung
adenocarcinoma
transcript
1
(MALAT-1)
influences
crucial
hallmarks
through
intricate
molecular
mechanisms,
including
proliferation,
invasion,
angiogenesis,
apoptosis,
the
epithelial-mesenchymal
transition
(EMT).
The
current
article
highlights
involvement
of
MALAT-1
in
drug
resistance,
making
it
a
potential
target
overcome
chemotherapy
refractoriness.
It
discusses
impact
on
immunomodulatory
molecules,
such
as
major
histocompatibility
complex
(MHC)
PD-L1,
leading
immune
evasion
hindering
anti-tumor
responses.
also
plays
significant
role
immunology
by
regulating
diverse
cell
populations.
In
summary,
is
versatile
regulator,
influencing
tumorigenesis,
chemoresistance,
immunotherapy
Understanding
its
precise
mechanisms
developing
targeted
therapies,
therapeutic
strategies
targeting
show
promise
improving
treatment
outcomes.
However,
further
research
needed
fully
uncover
biology
translate
these
findings
into
clinical
applications.
Non-coding RNA Research,
Год журнала:
2024,
Номер
9(4), С. 1222 - 1234
Опубликована: Май 20, 2024
Ferroptosis,
a
form
of
regulated
cell
death,
has
emerged
as
crucial
process
in
diverse
pathophysiological
states,
encompassing
cancer,
neurodegenerative
ailments,
and
ischemia-reperfusion
injury.
The
glutathione
(GSH)-dependent
lipid
peroxidation
pathway,
chiefly
governed
by
peroxidase
4
(GPX4),
assumes
an
essential
part
driving
ferroptosis.
GPX4,
the
principal
orchestrator
ferroptosis,
garnered
significant
attention
across
cardiovascular,
neuroscience
domains
over
past
decade.
Noteworthy
investigations
have
elucidated
indispensable
functions
ferroptosis
numerous
diseases,
including
tumorigenesis,
wherein
robust
within
cells
can
impede
tumor
advancement.
Recent
research
underscored
complex
regulatory
role
non-coding
RNAs
(ncRNAs)
regulating
GSH-GPX4
network,
thus
influencing
cellular
susceptibility
to
This
exhaustive
review
endeavors
probe
into
multifaceted
processes
which
ncRNAs
control
network
Specifically,
we
delve
miRNAs,
lncRNAs,
circRNAs
GPX4
expression
impacting
Moreover,
discuss
clinical
implications
dysregulated
interactions
between
several
conditions,
underscoring
their
capacity
viable
targets
for
therapeutic
intervention.
Additionally,
explores
emerging
strategies
aimed
at
targeting
modulate
pathway
manipulate
advantage.
A
comprehensive
understanding
these
intricate
networks
furnishes
insights
innovative
avenues
diseases
associated
with
perturbed
thereby
laying
groundwork
interventions
ferroptosis-related
pathological
conditions.
Heliyon,
Год журнала:
2024,
Номер
10(5), С. e27207 - e27207
Опубликована: Март 1, 2024
Cancer
drug
resistance
stands
as
a
formidable
obstacle
in
the
relentless
fight
against
top
five
prevalent
cancers:
breast,
lung,
colorectal,
prostate,
and
gastric
cancers.
These
malignancies
collectively
account
for
significant
portion
of
cancer-related
deaths
worldwide.
In
recent
years,
long
non-coding
RNAs
(lncRNAs)
have
emerged
pivotal
players
intricate
landscape
cancer
biology,
their
roles
driving
are
steadily
coming
to
light.
This
comprehensive
review
seeks
underscore
paramount
significance
lncRNAs
orchestrating
across
spectrum
different
drugs,
including
platinum
drugs
(DDP),
tamoxifen,
trastuzumab,
5-fluorouracil
(5-FU),
paclitaxel
(PTX),
Androgen
Deprivation
Therapy
(ADT)
most
types
cancer.
It
delves
into
multifaceted
mechanisms
through
which
exert
influence
on
resistance,
shedding
light
regulatory
various
facets
biology.
A
understanding
these
lncRNA-mediated
may
pave
way
more
effective
personalized
treatment
strategies,
ultimately
improving
patient
outcomes
challenging
malignancies.
Naunyn-Schmiedeberg s Archives of Pharmacology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 18, 2025
Abstract
Globally,
the
incidence
and
death
rates
associated
with
cancer
persist
in
rising,
despite
considerable
advancements
therapy.
Although
some
malignancies
are
manageable
by
a
mix
of
chemotherapy,
surgery,
radiation,
targeted
therapy,
most
malignant
tumors
either
exhibit
poor
responsiveness
to
early
identification
or
endure
post-treatment
survival.
The
prognosis
for
prostate
(PCa)
is
unfavorable
since
it
perilous
lethal
malignancy.
capacity
phytochemical
nutraceutical
chemicals
repress
oncogenic
lncRNAs
activate
tumor
suppressor
has
garnered
significant
attention
as
possible
strategy
diminish
development,
proliferation,
metastasis,
invasion
cells.
A
potential
technique
treat
enhance
sensitivity
cells
existing
conventional
therapies
use
phytochemicals
anticancer
characteristics.
Functional
studies
indicate
that
modulate
drug
resistance,
stemness,
invasion,
angiogenesis,
proliferation
via
interactions
suppressors
oncoproteins.
Among
them,
numerous
lncRNAs,
such
HOTAIR,
PlncRNA1,
GAS5,
MEG3,
LincRNA-21,
POTEF-AS1,
support
development
PCa
through
many
molecular
mechanisms,
including
modulation
regulation
various
signal
pathways
like
PI3K/Akt,
Bax/Caspase
3,
P53,
MAPK
cascade,
TGF-β1.
Other
particular,
MALAT-1,
CCAT2,
DANCR,
LncRNA-ATB,
ZEB1-AS1,
SChLAP1,
H19,
key
players
regulating
aforementioned
processes.
Natural
substances
have
shown
promising
benefits
against
altering
essential
signaling
pathways.
overexpression
advanced
TNM
stage,
chemoresistance,
reduced
LncRNAs
possess
crucial
clinical
transitional
implications
PCa,
diagnostic
prognostic
biomarkers,
well
medicinal
targets.
To
impede
progression
beneficial
target
aberrant
long
non-coding
RNAs
using
antisense
oligonucleotides
small
interfering
(siRNAs).
This
prevents
them
from
transmitting
harmful
messages.
In
summary,
several
precision
medicine
approaches
may
be
used
rectify
dysfunctional
lncRNA
regulatory
circuits,
so
improving
detection
eventually
facilitating
conquest
this
disease.
Due
their
presence
biological
fluids
tissues,
they
serve
novel
biomarkers.
Enhancing
treatments
mitigates
resistance
chemotherapy
radiation.
