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: EC:2.5.1.18 (
glutathione S-transferase
)
22,582
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Rationale
: As a component of GINS complex,
GINS4
is essential for initiating DNA replication and elongation of the cell cycle G1/S phase in eukaryotes and plays a vital role in normal physiological processes. However, the precise functions and regulation mechanisms of
GINS4
in human tumors remain elusive.
Methods
:
GINS4
expression was analyzed in gastric cancer tissues by qRT-PCR and western blotting, and its clinical relevance was studied using TMA. The biological functions of
GINS4
were detected
in vitro
and
in vivo
. cDNA array, co-IP,
GST
pull-down and GTPase activation assays were performed to investigate the downstream regulation mechanism of
GINS4
. Upstream regulation mechanism of
GINS4
was explored and demonstrated by circRNA sequencing, bioinformatics analysis, luciferase reporter assay and rescue experiments.
Results
: Strikingly high
GINS4
expression was detected in gastric cancer tissues and correlated with poor differentiation, advanced tumor stage, invasion depth and lymph node metastasis.
GINS4
promoted cell growth and metastasis
in vitro
and
in vivo
, and suppressed cell apoptosis
in vitro
. Mechanistically,
GINS4
activated Rac1/CDC42 through directly binding to Rac1/CDC42, thereby activating their downstream pathways. Furthermore, circMLLT10 acts as a miR-509-3-5p sponge to attenuate its repressive effect on target
GINS4
. In addition, circMLLT10 promoted cell growth and metastasis and suppressed cell apoptosis, whereas miR-509-3-5p inhibited cell growth and metastasis and promoted cell apoptosis.
Conclusion
: The findings indicate for the first time that the novel
GINS4
axis promotes gastric cancer cell growth and progression by activating Rac1 and CDC42.
GINS4
may be a promising biomarker and target for diagnosis and treatment of gastric cancer.
...
PMID:The novel GINS4 axis promotes gastric cancer growth and progression by activating Rac1 and CDC42. 3175 97
