Exportin XPO7 acts as an oncogenic factor in prostate cancer via upregulation of TCF3

Purpose: As a nuclear transport protein, XPO7 has been observed to show abnormal expression in various types of human cancers. However, the role of XPO7 in PCa remains elusive.

Methods: Here, in this study, immunohistochemistry and bioinformatics were used to determine the expression pattern and prognostic significance of XPO7. To investigate the functions of XPO7 in vitro and in vivo, we knocked down XPO7 in PCa cell lines and established xenograft mice models. Then, we used multiple experiments to determine the cell proliferation, migration, invasion, cell cycle and EMT in PCa cells after XPO7 modulation. Mechanistically, we conducted RNA-seq and identified the regulating effect of XPO7 on cell cycle-related and PI3K-AKT pathways. Furthermore, we assessed the regulating correlation between XPO7 and TCF3 and verified by a series of rescue experiments.

Results: We found a higher XPO7 expression in prostate cancer tissues and predicted a poorer prognosis of prostate cancer. Then, we further revealed that the ectopic expression of XPO7 in PCa cells facilitated cells proliferation, migration, cell cycle progression and EMT in vitro and promoted tumor growth in vivo. Mechanistically, we conducted RNA-seq and identified the regulating effect of XPO7 on cell cycle-related and PI3K-AKT pathways. Furthermore, a significantly positive correlation was discovered between the expression of XPO7 and TCF3. In addition, XPO7 may regulate PCa through mediating TCF3 expression. TCF3 depletion could alleviate the influence of XPO7 overexpression on malignant phenotypes of PCa cells.

Conclusions: These findings indicate that XPO7 promotes PCa initiation and progression and that targeting XPO7 might be therapeutically beneficial to patients with PCa.