ABSTRACT
@#[Abstract]
Objective:
To explore the effect and mechanism of
splicing factor 3b subunit 6 (SF3b6) on the proliferation,
apoptosis, invasion and migration of
gastric cancer cells.
Methods:
Tissue microarrays were used to detect the expression of SF3b6 in
gastric cancer tissues and adjacent
tissues. WB and qPCR were used to detect the expression of SF3b6 in normal immortalized gastric
epithelial cells (GES-1) and
gastric cancer cell lines (HGC27, AGS, BGC823, MGC803, SGC7901, MKN45). AGS and MGC803
cells were transfected with SF3b6
siRNA, and BGC823 and SGC7901
cells were transfected with SF3b6 over-expression
plasmid for functional experiments.
CCK-8 assay was used to detect the
regulation of SF3b6 on the proliferation of
gastric cancer cells; Transwell migration and invasion experiments were used to detect the effect of SF3b6 on the migration and invasion of
gastric cancer cells;
Flow cytometry was used to detect
cell apoptosis; and WB was adopted to detect expressions of
apoptosis and migration-related molecules and MAPK signaling pathway associated
proteins.
Results:
The expression level of SF3b6 in
gastric cancer MGC803 and AGS
cells was significantly higher while in BGC823 and SGC7901
cells was significantly lower than that in normal gastric epithelial GES-1
cells (P<0.05 or P<0.01). SF3b6 knockdown inhibited the proliferation, migration and invasion, but promoted
cell apoptosis of
gastric cancer cell lines AGS and MGC803 (P<0.05 or P<0.01); However, over-expression of SF3b6 promoted the proliferation, migration and invasion of
gastric cancer cell lines BGC823 and SGC7901 (P<0.05 or P<0.01). Mechanism study showed that SF3b6 knockdown promoted the activation of JNK and p38 and expression of
apoptosis-related
protein cleaved
caspase-9, cleaved PARP and Bax (P<0.05 or P<0.01), and meanwhile inhibited the process of epithelial to mesenchymal transition (EMT) in
gastric cancer cells.
Conclusion:
The
splicing factor SF3b6 enhances
cell proliferation and migration via MAPK signaling pathway, thereby promoting
tumor progression.