Germ cell-specific gene 2 accelerates cell cycle in epithelial ovarian cancer by inhibiting GSK3-p27 cascade

Epithelial ovarian cancer (EOC) is one of the most common malignant gynecological tumors with rapid growth potential and poor prognosis, however, the molecular mechanism underlying its outgrowth remained elusive. Germ cell-specific gene 2 (GSG2) was previously reported to be highly expressed in ovarian cancer and was essential for the growth of EOC. In this study, GSG2-knockdown cells and GSG2-overexpress cells were established through lentivirus-mediated transfection with Human ovarian cancer cells HO8910 and SKOV3. Knockdown of GSG2 inhibited cell proliferation and induced G2/M phase arrest in EOC. Interestingly, the expression of p27, a well-known regulator of the cell cycle showed a most significant increase after GSG2 knockdown. Further phosphorylation-protein array demonstrated the phosphorylation of GSK3 alpha Ser21 decreased in GSG2-knockdown cells to the most extent. Notably, inhibiting GSK3 alpha activity effectively rescued GSG2 knockdown's suppression on cell cycle as well as p27 expression in EOC. Our study substantiates that GSG2 is able to phosphorylate GSK3 alpha at Ser21 and then leads to the reduction of p27 expression, resulting in cell cycle acceleration and cell proliferation promotion. Thus, GSG2 may have the potential to become a promising target in EOC.