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CEP55 predicts the poor prognosis and promotes tumorigenesis in endometrial cancer by regulating the Foxo1 signaling

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Abstract

Endometrial cancer is a common gynecologic cancer, which is relevant to many differentially expressed genes. Centrosomal protein 55 (CEP55) was proved to be aberrantly expressed in several cancers. However, the function of CEP55 in endometrial cancer remains largely uncertain. The differentially expressed genes in endometrial cancer were analyzed by GEO datasets. CEP55 expression and its correlation to aggressive behaviors and diagnosis were analyzed by TCGA and the Human Protein Atlas databases. The association between CEP55 expression and 5-year overall survival in endometrial cancer was predicted using Kaplan–Meier Plotter database. Cell proliferation and apoptosis were determined by western blotting, EdU staining, TUNEL staining, and LDH release. CEP55-related targets were predicted by LinkedOmics and analyzed by KEGG pathway analysis using KOBAS. Foxo1 level was detected by western blotting. CEP55 expression was increased in endometrial cancer. The upregulated CEP55 was associated with tumor invasion, histologic grade, histological type and poor prognosis in endometrial cancer. CEP55 knockdown decreased PCNA and CDK2 levels and inhibited cell proliferation. Moreover, CEP55 downregulation promoted cell apoptosis, LDH release and increased cl-caspase-3/caspase-3 level. CEP55-related targets were enriched in Foxo1 signaling. CEP55 silencing increased the transcription activity of Foxo1. Inhibition of Foxo1 activity reversed the effect of CEP55 knockdown on cell proliferation and apoptosis. In conclusion, CEP55 knockdown repressed cell proliferation and facilitated apoptosis by regulating the Foxo1 signaling in endometrial cancer.

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Data availability

The data analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Gynecology, Nanyang First People’s Hospital, No. 12 Renmin Road, Nanyang, 473004, Henan, China

    Xinping Zhang, Enping Li, Tianyun Shi & He Chen

  2. Department of Medical Oncology, Nanyang First People’s Hospital, Nanyang, 473004, Henan, China

    Quanxiao Xu

Authors
  1. Xinping Zhang
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  2. Quanxiao Xu
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  3. Enping Li
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  4. Tianyun Shi
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  5. He Chen
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Contributions

HC designed the study and wrote the manuscript. XZ and QX performed the experiments. EL and TS collected and analyzed the data.

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Correspondence to He Chen.

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All authors have no conflicts of interest.

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Specimen collection was conducted in accordance with the ethics guidelines for the use of human material and approved by the Ethics Committee of the Nanyang First People’s Hospital.

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Zhang, X., Xu, Q., Li, E. et al. CEP55 predicts the poor prognosis and promotes tumorigenesis in endometrial cancer by regulating the Foxo1 signaling. Mol Cell Biochem 478, 1561–1571 (2023). https://doi.org/10.1007/s11010-022-04607-w

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  • DOI: https://doi.org/10.1007/s11010-022-04607-w

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