Oncogenic role of ALX3 in cervical cancer cells through KDM2B-mediated histone demethylation of CDC25A

Abstract

Background 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. Methods A 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. Results CDC25A 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. Conclusion This 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.

Identification and characterization of differentially expressed genes in cervical cancer: insights from transcriptomic analysis

“…These hub genes, such as HJURP, CDC25C, NCAPH, OIP5, CDC25A, DTL, DLGAP5, CENPF, ASPM and CDCA3, have been associated with cell division, DNA replication, and cell cycle regulation, indicating their importance in cervical carcinogenesis. Despite what is mentioned above (20), it has been evident that changes in the expression of CDC25C are closely related to tumorigenesis and tumor development and can be used as a potential target for cancer treatment (21). All these findings solidify our results.…”

“…For instance, NEK2, a serine/threonine kinase involved in mitosis, has been linked to chromosome instability, tumor progression, and metastasis in cervical cancer (19). Additionally, the downregulation of CDC25A in ME180 and C33A cells has been shown to impede cell proliferation, arrest cell cycle progression, and induce cell apoptosis (20).…”

DNA Methylation Biomarkers as Prediction Tools for Therapeutic Response and Prognosis in Intermediate-Stage Hepatocellular Carcinoma

“…It is also possible that these genes could be used as prognostic markers by which to predict the survival of HCC patients with a high degree of specificity. ALX3 is a member of the homeobox family with oncogenic potential in cervical squamous cell carcinoma through the transactivation of CDC25A by recruiting lysine demethylase 2B [ 33 ]. The methylation of ALX3 has been associated with neuroblastoma, colorectal carcinoma, and HCC [ 34 , 35 ].…”