Knockdown of PVT1 inhibits cell proliferation in luminal and basal-like breast cancer subtypes by activating LATS2/Hippo signaling pathway
Abstract
Background:
Breast
cancer
(BC)
is
a
malignant
tumor
seriously
threatening
women’s
health,
while
current
approaches
to
BC
treatment
are
challenged
by
the
existence
of
drug
resistance.
Combination
strategies
targeted
therapy
have
been
successfully
applied
in
clinical
treatment.
However,
whether
there
exist
critical
long
non-coding
RNAs
(lncRNAs)
responsible
for
pathogenesis
and
representing
promising
candidates
combined
remains
an
issue.
Methods:
Public
databases
bioinformatic
methods
were
used
identify
lncRNAs
abnormally
expressed
among
different
subtypes
BC.
The
expression
level
PVT1
was
verified
collected
samples
representative
cell
lines.
role
proliferation
examined
using
MTS,
plate
clone
formation,
EdU
flow
cytometry
assay
after
small
interfering
RNA
(siRNA)
sequencing
performed
investigate
potential
molecular
events
regulated
PVT1.
Western
blot
immunofluorescence
experiments
verify
activation
LATS2/Hippo
signaling
pathway
knockdown.
In
addition,
its
confirmed
mediate
function
through
rescue
assay.
regulatory
effect
on
LATS2
investigated
mRNA
stability
experiments.
Results:
The
tissues
luminal
basal-like
significantly
higher
than
that
paracancerous
tissues.
knockdown
substantially
inhibited
cells
both
subtypes.
revealed
Hippo
might
be
downstream
target
After
knockdown,
protein
elevated
which
further
decreased
distribution
YAP
nucleus,
indicating
pathway.
inhibitory
could
attenuated
simultaneous
LATS2.
Furthermore,
demonstrated
slow
down
degradation
rate
mRNA.
Conclusions:
PVT1
Knockdown
inhibit
these
two
partly
activating
Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown
Published: April 9, 2025
Language: Английский