Abstract
Minichromosome maintenance 3 (MCM3) protein has been widely studied due to its essential role in DNA replication. In addition, it is overexpressed in several human tumor types. However, the role of this protein in renal cell carcinoma (RCC) is not widely known. In this study, we demonstrated that polo-like kinase 1 (PLK1)-mediated MCM3 phosphorylation regulates proliferation and apoptosis in RCC. Our results confirm that PLK1 and phospho-MCM3 (p-MCM3) are highly expressed in renal cell carcinoma. The expression of PLK1 is closely related to the clinical characteristics of renal cell carcinoma. They play important roles in the proliferation and apoptosis of RCC. In vitro, after overexpression of PLK1 or MCM3, the proliferation of RCC cells was significantly enhanced and cell apoptosis was inhibited, while after knockout, the proliferation of RCC cells was weakened and cell apoptosis was promoted. In addition, Mn2+-Phos-tag SDS–PAGE, western blotting, and immunofluorescence were utilized to determine that MCM3 is a physiological substrate of PLK1, which is phosphorylated on serine 112 (Ser112) in a PLK1-dependent manner. PLK1-mediated MCM3 phosphorylation promotes RCC cell cycle proliferation and suppresses apoptosis in vitro. Moreover, we found that PLK1-mediated MCM3 phosphorylation induced cellular proliferation and decreased apoptosis, as well as tumor growth in mice. Overall, we conclude that PLK1-mediated MCM3 phosphorylation is a novel mechanism to regulate RCC proliferation and apoptosis.
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Change history
31 March 2022
A Correction to this paper has been published: https://doi.org/10.1038/s41417-022-00458-1
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Funding
This work was supported by National Natural Science Fund (Grant No. 81672525), the Project of Liaoning Distinguished Professor (Grant No. [2012]145), Liaoning Natural Science Fund (Grant No. 201602830), Shenyang Plan Project of Science and Technology (Grant No. F17-230-9-08) and Shenyang clinical medicine research center (Grant No. [2017]76), China Medical University’s 2017 discipline promotion program (Grant No. 2017XK08), China Medical University’s 2018 discipline promotion program, 2017 National Key R&D Program Key Projects of Precision Medical Research (2017YFC0908000). Funding agency did not participate in the design of the study and collection, analysis and interpretation of data and in writing the manuscript.
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Gao, Z., Man, X., Li, Z. et al. PLK1 promotes proliferation and suppresses apoptosis of renal cell carcinoma cells by phosphorylating MCM3. Cancer Gene Ther 27, 412–423 (2020). https://doi.org/10.1038/s41417-019-0094-x
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DOI: https://doi.org/10.1038/s41417-019-0094-x
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