Abstract
Tumor invasion, metastasis, and recrudescence remain a considerable challenge in the treatment of gastric cancer (GC). Herein we first identified that RNA binding protein fox-1 homolog 3 (RBFOX3) was markedly overexpressed in GC tissues and negatively linked to the survival rate of GC patients. RBFOX3 promoted cell division and cell cycle progression in vitro and in vivo. Furthermore, RBFOX3 increased the cell invasion and migration ability. The suppression of GC cell multiplication and invasion, caused by silencing of RBFOX3, was rescued by HTERT overexpression. Additionally, RBFOX3 augmented the resistance of GC cells to 5-fluorouracil by repressing RBFOX3. Mechanistically, the exogenous up-regulation of RBFOX3 triggered promoter activity and HTERT expression, thereby enhancing the division and the development of GC cells. Further co-immunoprecipitation tests revealed that RBFOX3 bound to AP-2β to modulate HTERT expression. In conclusion, our study indicates that a high expression of RBFOX3 promotes GC progression and development and predicts worse prognosis. Collectively, these results indicate that the RBFOX3/AP-2β/HTERT signaling pathway can be therapeutically targeted to prevent and treat GC recurrence and metastasis.
Highlights
Tumor invasion, metastasis, and recrudescence remain a considerable challenge in the treatment of gastric cancer (GC)
D We find that RNA binding protein fox-1 homolog 3 (RBFOX3) is significantly up-regulated in GC
To elucidate the factors driving RBFOX3-mediated metastasis, knockdown cells treated with 5-Fu was significantly lower relative we evaluated the expression of some oncogenes and tumor to that of mock knockdown cells treated with 5-Fu
Summary
The transfected GC cells were seeded in six-well plates and imaged 0 and 24 h later to monitor migration. (A–C) The wound healing assay was performed to investigate the horizontal E migration of cells following RBFOX3 overexpression or silencing in SGC-7901 (left panel) and MGC-803 cells (middle panel). (D–F) Results of the vertical migration and the invasion capacities of cells following RBFOX3 overexpression or silencing in SGC-7901 (left panel) and MGC-803 (middle panel) cells. T the protein expression of metastasis-related proteins following RBFOX3 overexpression or silencing in SGC-7901 and MGC-803 cells. R Real-Time PCR added into the beads and heated at 4◦C for 5 min
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