Networking Salt Inducible Kinase 1 Regulatory Perturbations on Type 2 Diabetes- Breast Cancer Co-Morbidity Associated Molecular Bridge
The EuroBiotech Journal,
Год журнала:
2025,
Номер
9(1), С. 90 - 106
Опубликована: Янв. 1, 2025
Abstract
Type
2
diabetes
mellitus
(T2DM)
is
associated
with
a
16%
elevated
risk
of
breast
cancer
(BC).
However,
the
underlying
molecular
mechanisms
are
yet
to
be
fully
understood.
T2DM
and
BC
multifactorial
polygenic
in
nature,
hence
it
plausible
an
interplay
between
various
signalling
pathways
wired
into
co-morbidity
program.
Salt
inducible
kinase
1
(SIK1)
was
previously
validated
silico
as
hub
gene
for
T2DM-BC
crosstalk.
To
probe
its
functional
niche
within
co-diseasome,
this
study
constructed
subjected
SIK1
regulome
network
modelling.
Gene
mutations,
transcription
factors
(TF),
proteins
microRNA
(miRNA)
protein-protein
interactions
(PPIs)
were
extracted
from
MuTarget
EnrichR,
respectively.
TF-miRNA
regulatory
iteration
studied
on
Cytoscape,
identify
143
PPIs.
Interestingly,
these
enriched
KEGG
PI3K-AKT
signalling,
cancer.
Furthermore,
ClinVar
disease
terms
particularly
included
BC,
highlighting
their
potential
implication
co-morbidity.
Top
genes
TP53,
EP300,
AKT1,
CREB1,
HIF1A,
EGFR,
SMARCA4,
HDAC2,
NFKB1
HDAC5
.
Prospective
studies
potentiating
TP53
,
context
dynamics
may
provide
further
insights
links
tying
BC.
Язык: Английский
Targeting p70S6K1 Inhibits Glycated Albumin-Induced Triple-Negative Breast Cancer Cell Invasion and Overexpression of Galectin-3, a Potential Prognostic Marker in Diabetic Patients with Invasive Breast Cancer
Biomedicines,
Год журнала:
2025,
Номер
13(3), С. 612 - 612
Опубликована: Март 3, 2025
Background:
There
is
an
urgent
need
to
identify
new
biomarkers
for
early
diagnosis
and
development
of
therapeutic
strategies
diabetes
mellitus
(DM)
patients
who
have
invasive
breast
cancer
(BC).
We
previously
reported
the
increased
activated
form
70
kDa
ribosomal
protein
S6
kinase
1
(phospho-p70S6K1)
in
a
triple-negative
BC
(TNBC)
cell
line
MDA-MB-231
exposed
glycated
albumin
(GA)
ductal
carcinoma
tissues
from
T2DM
patients,
compared
untreated
cells
their
non-diabetic
counterparts,
respectively.
Objective:
aimed
explore
function
p70S6K1
GA-promoted
TNBC
progression.
Methods:
By
employing
small
interference
(si)RNA
technology
or
blocking
its
activity
using
specific
pharmacological
inhibitor,
we
monitored
invasion
Transwell®
inserts
expression
levels
signaling
proteins
cancer-related
Western
blot.
Results:
In
silico
analysis
revealed
that
high
mRNA
were
associated
with
unfavorable
prognosis
progression
advanced
stages
DM
patients.
The
downregulation/blockade
inhibited
phosphorylation
ERK1/2,
downstream
effector,
key
oncogenic
protein,
suppression
GA-upregulated
proteins,
including
enolase-2,
capping
CapG,
galectin-3,
cathepsin
D,
was
observed
after
downregulation/blockade.
Further
validation
analyses
gene
galectin-3
resulting
poor
overall
survival
disease-free
survival.
Conclusions:
Targeting
may
present
valuable
strategy,
while
could
serve
as
potential
prognostic
biomarker
Язык: Английский