CDK12 regulates angiogenesis of advanced prostate cancer by IGFBP3

Zhong,Kun; Luo,Wenwu; Li,Nan; Tan,Xin; Li,Yuqing; Yin,Shiyuan; Huang,Yuhang; Fang,Linna; Ma,Wei; Cai,Yongping; Yin,Yu

doi:10.3892/ijo.2024.5608

CDK12 regulates angiogenesis of advanced prostate cancer by IGFBP3

Authors:
- Kun Zhong
- Wenwu Luo
- Nan Li
- Xin Tan
- Yuqing Li
- Shiyuan Yin
- Yuhang Huang
- Linna Fang
- Wei Ma
- Yongping Cai
- Yu Yin
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Affiliations: Department of Pathology, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Nephrology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
Published online on: January 4, 2024 https://doi.org/10.3892/ijo.2024.5608
Article Number: 20
Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Prostate cancer (PCa) is a prevalent malignancy among men, with a majority of patients presenting with distant metastases at the time of initial diagnosis. These patients are at a heightened risk of developing more aggressive castration‑resistant PCa following androgen deprivation therapy, which poses a greater challenge for treatment. Notably, the inhibition of tumor angiogenesis should not be considered an ineffective treatment strategy. The regulatory role of CDK12 in transcriptional and post‑transcriptional processes is essential for the proper functioning of various cellular processes. In the present study, the expression of CDK12 was first knocked down in cells using CRISPR or siRNA technology. Subsequently, RNA‑seq analysis, co‑immunoprecipitation, western blotting, reverse transcription‑quantitative polymerase chain reaction and the LinkedOmics database were employed to reveal that CDK12 inhibits insulin like growth factor binding protein 3 (IGFBP3). Western blot analysis also demonstrated that CDK12 promoted VEGFA expression by inhibiting IGFBP3, which involves the Akt signaling pathway. Then, CDK12 was found to promote PCa cell proliferation, cell migration and angiogenesis by inhibiting IGFBP3 through cell proliferation assays, cell migration assays and tube formation assays, respectively. Finally, animal experiments were performed for in vivo validation. It was concluded that CDK12 promoted PCa and its angiogenesis by inhibiting IGFBP3.

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