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CDK12 Promotes the Proliferation, Migration, and Angiogenesis of Gastric Carcinoma via Activating the PI3K/AKT/mTOR Signaling Pathway

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Abstract

Cyclin-dependent kinase 12 (CDK12) has been found to regulate tumor progression. However, its function in gastric carcinoma (GC) remains controversial. This work aimed to explore the exact effect of CDK12 on GC progression. We detected the expression of CDK12 in GC cells and normal gastric mucosal epithelial cells. Then CDK12 function on GC cell proliferation, migration, and angiogenesis was researched by colony formation experiment, Transwell experiment, and angiogenesis assay. Moreover, CDK12 effect on the PI3K/AKT/mTOR pathway activity was explored by western blot. Further, we used LY294002 (10 μM) to treat GC cells to verify whether CDK12 regulates GC progression by activating the PI3K/AKT/mTOR pathway. Additionally, CDK12 effect on the expression of prognostic factors of GC was detected by western blot, including alkaline phosphatase (ALP) and Ki67. Quantitative real-time polymerase chain reaction and western blot were utilized to evaluate the expression of mRNAs and proteins. As a result, CDK12 was upregulated in GC cells. CDK12 overexpression facilitated the proliferation, migration, and angiogenesis of GC cells. However, CDK12 silencing showed an opposite result. CDK12 overexpression activated the PI3K/AKT/mTOR pathway, but CDK12 silencing inactivated it in GC cells. The blockage of the PI3K/AKT/mTOR pathway induced by LY294002 treatment counteracted the promotion of CDK12 on the proliferation, migration, and angiogenesis of GC. Further, CDK12 silencing suppressed the expression of ALP and Ki67 proteins in GC cells. Taken together, CDK12 promotes the proliferation, migration, and angiogenesis of GC by activating the PI3K/AKT/mTOR pathway. It may be a novel target for GC treatment.

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Funding

This work was supported by the National Cancer Center Climbing Fund (NCC201801B002).

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Authors and Affiliations

  1. The Second Department of Comprehensive Medicine, Cancer Hospital of Huanxing Chaoyang District, Beijing, No. 1, Lujiaying South Lijia, Shibailidian Township, Chaoyang District, Beijing, 100023, China

    Li-zhen Gao, Jun-qing Wang, Jun-lin Chen, Xue-lin Zhang, Man-man Zhang, Su-ling Wang & Chen Zhao

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  1. Li-zhen Gao
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  2. Jun-qing Wang
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  3. Jun-lin Chen
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  4. Xue-lin Zhang
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  7. Chen Zhao
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Jun-lin Chen, Xue-lin Zhang, Man-man Zhang, Su-ling Wang, and Chen Zhao. The first draft of the manuscript was written by Li-zhen Gao and Jun-qing Wang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Li-zhen Gao or Jun-qing Wang.

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Li-zhen Gao and Jun-qing Wang contributed equally to this study.

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Gao, Lz., Wang, Jq., Chen, Jl. et al. CDK12 Promotes the Proliferation, Migration, and Angiogenesis of Gastric Carcinoma via Activating the PI3K/AKT/mTOR Signaling Pathway. Appl Biochem Biotechnol 195, 6913–6926 (2023). https://doi.org/10.1007/s12010-023-04436-7

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  • DOI: https://doi.org/10.1007/s12010-023-04436-7

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