Abstract
BackgroundCell division cycle 25A (CDC25A) is a well-recognized regulator of cell cycle progression and is involved in cancer development. This work focused on the function of CDC25A in cervical cancer cell growth and the molecules involved.MethodsA GEO dataset GSE63514 comprising data of cervical squamous cell carcinoma (CSCC) tissues was used to screen the aberrantly expressed genes in cervical cancer. The CDC25A expression in cancer and normal tissues was predicted in the GEPIA database and that in CSCC and normal cells was determined by RT-qPCR and western blot assays. Downregulation of CDC25A was introduced in CSCC cells to explore its function in cell growth and the cell cycle progression. The potential regulators of CDC25A activity and the possible involved signaling were explored.ResultsCDC25A was predicted to be overexpressed in CSCC, and high expression of CDC25A was observed in CSCC cells. Downregulation of CDC25A in ME180 and C33A cells reduced cell proliferation and blocked cell cycle progression, and it increased cell apoptosis. ALX3 was a positive regulator of CDC25A through transcription promotion. It recruited a histone demethylase, lysine demethylase 2B (KDM2B), to the CDC25A promoter, which enhanced CDC25A expression through demethylation of H3k4me3. Overexpression of ALX3 in cells blocked the inhibitory effects of CDC25A silencing. CDC25A was found as a positive regulator of the PI3K/Akt signaling pathway.ConclusionThis study suggested that the ALX3 increased CDC25A expression through KDM2B-mediated demethylation of H3K4me3, which induced proliferation and cell cycle progression of cervical cancer cells.
Highlights
Cell division cycle 25A (CDC25A) is a well-recognized regulator of cell cycle progression and is involved in cancer development
CDC25A is highly expressed in cervical cancer samples First, the GSE63514 dataset, which comprises data of 24 cases of normal cervical epithelial tissues and 104 cases of Cervical squamous cell carcinoma (CSCC) tissues, was obtained from the Gene Expression Omnibus (GEO) database and analyzed using the R Limma package
To further validate the correlation between CDC25A and cervical cancer progression, we further explored the CDC25A expression in The Cancer Genome Atlas (TCGA)-CESC and GTEx-Cervix in the Gene Expression Profiling Interactive Analysis (GEPIA) database
Summary
Cell division cycle 25A (CDC25A) is a well-recognized regulator of cell cycle progression and is involved in cancer development. This work focused on the function of CDC25A in cervical cancer cell growth and the molecules involved. Cervical squamous cell carcinoma (CSCC) represents the most frequent type which accounts for approximately 80% of all cases of cervical cancer, and nearly 90% of these cases are caused by human papillomavirus (HPV) infection [2, 3]. Thanks to the increasing administration of HPV vaccines [4, 5], the incidence rate of cervical cancer is expected to experience a significant decline. A substantial increase in cervical cancer morbidity has been seen in China, which may be caused by the inadequate Papanicolaou test screening and less coverage of HPV vaccines [6]. Developing novel less-invasive options for cervical cancer treatment is of great significance
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