Upregulation of Pole2 Promotes Clear Cell Renal Cell Carcinoma Progression via AKT/mTOR Pathway and Predicts a Poor Prognosis

Abstract Background: Pole2 gene is a subunit of DNA polymerases localized in the nucleus, which commonly present in DNA repair. The effect of pole2 in renal cell carcinoma (RCC) still remain unclear. Here we investigate its clinical significance, function in RCC cells and possible mechanism of effect.Methods: Using TCGA database, we identified that up-regulation of pole2 is associated with poor prognosis in ccRCC. We analyzed association between pole2 expression and T stage or Fuhrman grade. Thus, we investigate the effects of pole2 down-regulation on proliferation, cell cycles, apoptosis and possible mechanism in cells using lentivirus vector with shPole2.Results: Our study showed overexpression of pole2 in ccRCC samples, compared with normal kidney tissues, moreover, high expression of it related to high Fuhrman grade, also may predict poor prognosis in patients with ccRCC (p < 0.05). In cultured cells, knockdown of pole2 would result in inhibit of cell proliferation, increase the apoptosis of cells and arrest cell cycle at S phase. Importantly, knockdown pole2 can lead to down-regulation of p-mTOR and p-AKT expression.Conclusion: Taken together, our findings suggest that overexpression of pole2 may promote tumorgenesis and progress of ccRCC via AKT/mTOR signaling.