Abstract

BackgroundCell 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.MethodsImmunohistochemical 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.ResultCyclin 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.ConclusionThese results suggest that high expression of cyclin H predicts the poor prognosis and promotes the growth of ovarian cancer by regulating the cell cycle.

Highlights

  • Cell cycle dysregulation plays a key role in the pathogenesis of malignant tumors

  • 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

  • Cyclin H, a member of the cyclin family, together with CDK7 and MAT1 forms the cyclin-dependent kinase (CDK)-activating kinase (CAK) trimeric complex, which is necessary for the regulation of cell cycle and proliferation

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Summary

Introduction

Cell cycle dysregulation plays a key role in the pathogenesis of malignant tumors. As a part of the CDKactivating 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. The expression of cell cycle regulators is linked to tumor development, prognosis, and treatment response [10]. Cyclin H, a member of the cyclin family, together with CDK7 and MAT1 forms the CDK-activating kinase (CAK) trimeric complex, which is necessary for the regulation of cell cycle and proliferation. The clinical significance and the biological function of cyclin H in ovarian cancer remains unclear

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