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RACGAP1 (Rac GTPase-activating protein 1) is correlated with tumor aggressiveness and poor prognosis, but the role of RACGAP1 in cervical cancer has not been fully reported. Analysis of RACGAP1 expression data in cervical cancer from the Cancer Genome Atlas (TCGA) database was carried out by GEPIA and UALCAN websites. In addition, the UALCAN database was used to identify the RACGAP1 positively correlated genes, which were used for the enrichment analysis. qRT-PCR, immunohistochemistry, western blot, and immunofluorescence were utilized to measure RACGAP1 expression in tissues and cells. Western blot, flow cytometry, MTT, and colony formation assays were applied to assess the effects of RACGAP1 on cell cycle, growth and viability in cervical cancer. Through bioinformatics analysis, we found that the level of RACGAP1 was aberrantly increased in cervical cancer, which was confirmed in cervical cancer tissues and cells. RACGAP1 associated genes, including CDC25C, were mainly enriched in cell cycle pathway, and RACGAP1 expression was negatively associated with CDC25C expression. RACGAP1 overexpression was related to patient's poor prognosis and promoted cervical cancer cell proliferation. Furthermore, RACGAP1 knockdown decreased the level of CDC2, p-CDC2, CDC25C, and Cyclin B1, inhibited proliferation and delayed cell cycle progression in cervical cancer cells. In mechanism, overexpression of CDC25C attenuated RACGAP1 knockdown-mediated cell growth inhibition and cell cycle arrest. Taken together, this study demonstrated that RACGAP1 was overexpressed in cervical cancer, and downregulation of RACGAP1 could inhibit the cervical cancer cell proliferation and cell cycle progression through regulating CDC25C expression. Copyright © 2022 Elsevier Ltd. All rights reserved.

Citation

Xiqin Ruan, Jun Jiang. RACGAP1 promotes proliferation and cell cycle progression by regulating CDC25C in cervical cancer cells. Tissue & cell. 2022 Jun;76:101804

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PMID: 35489195

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