Cyclin‑dependent kinase 1 disruption inhibits angiogenesis by inducing cell cycle arrest and apoptosis

Gao,Xin; Zhang,Yuan; Zhang,Rui; Zhao,Zichan; Zhang,Haorui; Wu,Jinhui; Shen,Wei; Zhong,Ming

doi:10.3892/etm.2019.7883

Cyclin‑dependent kinase 1 disruption inhibits angiogenesis by inducing cell cycle arrest and apoptosis

Authors:
- Xin Gao
- Yuan Zhang
- Rui Zhang
- Zichan Zhao
- Haorui Zhang
- Jinhui Wu
- Wei Shen
- Ming Zhong
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Affiliations: Department of Ophthalmology, Shanghai Changhai Hospital, Shanghai 200433, P.R. China, Company 6 of Basic Medical School, Second Military Medical University, Shanghai 200433, P.R. China
Published online on: August 13, 2019 https://doi.org/10.3892/etm.2019.7883
Pages: 3062-3070
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Angiogenesis is a complex process, which involves the sprouting of new blood vessels from pre‑existing vasculature. Pathological retinal angiogenesis can lead to vision loss and even blindness. Cyclin‑dependent kinase 1 (CDK1) is involved in regulation of the cell cycle and is reported to contribute to tumor progression. However, the role of CDK1 in retinal angiogenesis is largely unknown. The purpose of the present study was to investigate the role of CDK1 in retinal angiogenesis. Western blotting, reverse transcription‑quantitative PCR (RT‑qPCR) analysis, immunofluorescence and immunohistochemistry were used to evaluate the expression of CDK1 in pathological angiogenesis using an oxygen‑induced retinopathy (OIR) mouse model. Small interfering (si)RNA sequences against CDK1 were synthesized and incubated with retinal cells. The efficiency of knockdown was confirmed by western blot and RT‑qPCR assays. The effect of CDK1 siRNAs on angiogenesis in vitro was investigated using EdU cell proliferation, cell migration and tube formation assays. Subsequently, flow cytometry was used to assess the effects of CDK1 siRNAs on cell cycle distribution and on the induction of apoptosis. The expression levels of cell cycle‑ and apoptosis‑related genes were detected using western blotting. CDK1 was overexpressed in pathological retinal angiogenesis. CDK1 siRNAs inhibited human umbilical vein endothelial cell proliferation, migration and tube formation. The possible mechanisms involved the induction of cell cycle arrest at the G2/M phase and the induction of apoptosis via an increase in the expression levels of p21 and p53. In conclusion, the data indicated that CDK1 was overexpressed in the OIR model and that silencing of CDK1 inhibited angiogenesis in vitro. CDK1 may be a novel therapeutic target for pathological retinal angiogenesis.

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