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03-01-2024 | Cervical Cancer | Original Article

FOXM1 transcriptional regulation of RacGAP1 activates the PI3K/AKT signaling pathway to promote the proliferation, migration, and invasion of cervical cancer cells

Authors: Hongye Yao, Juan Li, Dan Zhou, Xiaotian Pan, Yaying Chu, Jun Yin

Published in: International Journal of Clinical Oncology | Issue 3/2024

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Abstract

Background

Cervical cancer (CC) is the most common gynecological tumor disease in women, which occurs at the junction of cervical squamous columnar epithelium. We investigated the effect and mechanism of transcription factor FOXM1 synergizing RacGAP1 in the proliferation, migration, and invasion of CC cells.

Methods

Here, we analyzed the correlation between FOXM1 and RacGAP1 and the clinicopathological features of 68 CC patients. RT-qPCR was used to assess FOXM1 and RacGAP1 mRNA expression in CC tissues and cells. Cell proliferation was assessed by CCK-8 and EDU assays. Transwell assay was applied to test migration and invasion. Cell apoptosis was evaluated utilizing flow cytometry. ChIP and dual-luciferase reporter assays confirmed the interaction of FOXM1 and RacGAP1. Protein levels of FOXM1 and RacGAP1, as well as PI3K/AKT, were analyzed by Western blot.

Results

FOXM1 expression was correlated with FIGO stage and histological grade, and RacGAP1 expression was correlated with histological grade. FOXM1 and RacGAP1 levels were increased in CC tissues, and higher expressed in human CC cell lines than that in an immortalized HPV-negative skin keratinocyte line (HaCaT). Depleted RacGAP1 suppressed CC cell proliferation, migration and invasion, and promoted apoptosis. RacGAP1 was a target gene of FOXM1, and FOXM1 positively regulated RacGAP1 expression. FOXM1 had a synergistic effect with RacGAP1 to exert oncogenic function in CC by activating the PI3K/AKT signaling.

Conclusion

FOXM1 cooperates with RacGAP1 to induce CC cell proliferation, migration and invasion, inhibit apoptosis, and regulate PI3K/AKT signaling to promote CC progression.
Appendix
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Metadata
Title
FOXM1 transcriptional regulation of RacGAP1 activates the PI3K/AKT signaling pathway to promote the proliferation, migration, and invasion of cervical cancer cells
Authors
Hongye Yao
Juan Li
Dan Zhou
Xiaotian Pan
Yaying Chu
Jun Yin
Publication date
03-01-2024
Publisher
Springer Nature Singapore
Published in
International Journal of Clinical Oncology / Issue 3/2024
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-023-02452-5

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