Background: Cell cycle dysregulation plays a key role in the pathogenesis of malignant tumors. As a part of the CDK-activating kinase (CAK) trimeric complex, cyclin H is necessary to regulate the cell cycle and proliferation. This investigation aims to characterize the clinical significance and the biological functions of cyclin H in ovarian cancer.
Methods: Immunohistochemical staining was performed on 60 ovarian cancer cases, and a correlation between cyclin H expression and the clinical characteristics of ovarian cancer was analyzed. The function of cyclin H in ovarian cancer was further explored using HO8910 cells and a subcutaneous xenograft model of nude mice.
Result: Cyclin H was slightly expressed in grade 1 ovarian cancer but highly expressed in grade 2 and grade 3 cancerous tissues. The Spearman’s rank correlation analysis showed that the expression of cyclin H is positively correlated with the tumor grade, the FIGO stage, histological grade, and the peritoneal metastasis of ovarian cancer and is also positively correlated with the Ki67 and p-CDK2 in ovarian cancer. Additionally, we found that the five-year survival rate was higher in patients expressing low cyclin H than those expressing high cyclin H. Further, knockdown of cyclin H was achieved using an shRNA in HO8910 ovarian cancer cell line. Silencing cyclin H resulted in a G1/S cell cycle arrest in ovarian cancer cells suppressing its growth. The Ki67 expression was also decreased in cyclin H silenced ovarian cancer.
Conclusion: These results suggest that high expression of cyclin H predicts the poor prognosis and promotes the growth of ovarian cancer by regulating the cell cycle.
Keywords: CDK2; Cell cycle; Cyclin H; Ovarian cancer.