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

Jinhong Qi, Li Zhou, Dongqing Li, Jingyuan Yang, He Wang, Huifang Cao, Yunlan Huang, Zhiming Zhang, Linlin Chang, Chenhao Zhu, Juntong Zhan, Yong Yuan

BMC cancer 2021 Jul 16

filter terms:

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. 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. 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. 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. © 2021. The Author(s).

Citation

Jinhong Qi, Li Zhou, Dongqing Li, Jingyuan Yang, He Wang, Huifang Cao, Yunlan Huang, Zhiming Zhang, Linlin Chang, Chenhao Zhu, Juntong Zhan, Yong Yuan. Oncogenic role of ALX3 in cervical cancer cells through KDM2B-mediated histone demethylation of CDC25A. BMC cancer. 2021 Jul 16;21(1):819