FXYD3 knockdown by small interfering RNA inhibits cell proliferation and migration of oral squamous cell carcinoma cells

Abstract

BACKGROUND: Oral squamous cell carcinoma (OSCC), the most common malignant neoplasm in oral cavity, is a significant worldwide public health threat. FXYD3 was reported to be overexpressed in prostate, breast, and pancreatic cancers, suggesting its role of carcinogenesis by providing a growth advantage, but downregulated in lung cancers comparing to the normal tissue. However, there have been no reports on the expression and role of FXYD3 in oral squamous cell carcinoma. METHODS: We generated two FXYD3-knockdown clones (SCC-4si and HO-1-U-1si) from the SCC-4 and HO-1-U-1 OSCC cell lines by transfection with small interfering RNA for FXYD3. Cell proliferation and in vitro migration assays were used to investigate the effect of FXYD3 downregulation on cell proliferation and migratory ability in SCC-4si and HO-1-U-1si. Immunohistochemistry was performed to evaluate the correlation between FXYD3 expression and proliferation in 60 OSCC tissue samples. RESULTS: The FXYD3-knockdown cells grew significantly slower than the control cells. SCC-4si cells proliferated at 35.7%, 60.9% and 62.7% of the rate of control cells at 24, 48, and 72 hours after transfection, respectively (P<0.05). Also, HO-1-U-1si cells did at 47.7%, 28.3% and 34.5%, respectively (P<0.05). FXYD3-knockdown cells showed reduced migratory ability. The migration percentages of SCC-4si cells were 37.2% and 38.4% after 24 and 48h, respectively, compared with the control cells (P<0.05). Also, those of HO-1-U-1si cells were 33.3% and 44.1%, respectively (P<0.05). OSCC showed significantly higher FXYD3 expression than normal mucosa (P<0.05). The group with strong expression of FXYD3 had significantly higher Ki-67 labelling index than that with weak expression in OSCC tissue samples (P<0.05). CONCLUSION: These results suggest that the downregulation of FXYD3 induces anti-proliferative and anti-migratory effects in OSCC and that FXYD3 might be a useful target molecule for the treatment of OSCC.