Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0017638 (
glioma
)
30,880
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Background:
The resistance of
glioma
patients to temozolomide (TMZ) treatment is a limiting factor in clinical treatment. Circular RNA HIPK3 (
circ-HIPK3
) was found to be highly expressed in
glioma
, however, the role and potential mechanism of exosomal
circ-HIPK3
from TMZ-resistant cells remain poorly unclear.
Methods:
Exosomes were characterized by transmission electron microscopy. The levels of all protein were detected by western blot. Expression levels of
circ-HIPK3
, microRNA-421 (
miR-421
), and
zinc finger protein of the cerebellum 5
(
ZIC5
) were measured by quantitative real-time polymerase chain reaction. The cell's 50% inhibitory concentration (IC
50
) of TMZ, apoptosis, and invasion were determined by methyl thiazolyl tetrazolium (MTT), flow cytometry, and Transwell assays, respectively. The correlation between
miR-421
and
circ-HIPK3
or
ZIC5
was identified by dual-reporter luciferase and RNA immunoprecipitation (RIP) assays. The xenograft model was established to explore the effect of
circ-HIPK3 in vivo
.
Results:
Circ-HIPK3
was obviously increased in TMZ-resistant
glioma
cells and their exosomes,
miR-421
, was downregulated in TMZ-resistant
glioma
.
Circ-HIPK3
directly targeted
miR-421
and their expressions were negatively correlated in
glioma
tissues. Besides,
circ-HIPK3
knockdown hampered the IC
50
of TMZ, cell invasion, TMZ resistance, and triggered cell apoptosis, whereas these effects were reversed by transfection of anti-miR-421.
ZIC5
was the target of
miR-421
and
ZIC5
overexpression weakened the inhibition effects of
miR-421
on cell progression and TMZ resistance. More importantly,
circ-HIPK3
depletion inhibited tumor growth by decreasing
ZIC5
through sponging
miR-421 in vivo
.
Conclusion:
Exosomal
circ-HIPK3
could promote cell progression and TMZ resistance by regulating
miR-421/ZIC5
axis in TMZ-resistant
glioma
.
...
PMID:Exosomal
Circ-HIPK3
Facilitates Tumor Progression and Temozolomide Resistance by Regulating
miR-421/ZIC5
Axis in Glioma. 3264 21
