The role of GADD45G methylation in endometrial cancer: Insights into CDK1/CCNB1 activation and therapeutic opportunities.

Autor: Wang C; Department of Gynecology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.; Department of Gynecology, Cangzhou People's Hospital, Cangzhou, Hebei, China., Shan S; Department of Gynecology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China., Li X; Department of Gynecology, Hebei General Hospital, Shijiazhuang, Hebei, China., Wang H; Department of Gynecology, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China., Qi J; Department of Gynecology, Hebei General Hospital, Shijiazhuang, Hebei, China., Zhao S; Department of Gynecology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Jazyk: angličtina
Zdroj: Journal of cancer research and therapeutics [J Cancer Res Ther] 2024 Aug 01; Vol. 20 (4), pp. 1214-1223. Date of Electronic Publication: 2024 Aug 29.
DOI: 10.4103/jcrt.jcrt_2103_23
Abstrakt: Introduction: Accumulating evidence suggests the significant involvement of GADD45G in the development of various cancers. This study investigates GADD45G's involvement and methylation status in endometrial cancer (EC), along with molecular mechanisms and potential therapies.
Methods: The expression of GADD45G in EC tissues and controls was evaluated using RNA-seq, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting (WB). Methylation-specific PCR (MSP) evaluated GADD45G's methylation status. Protein-protein interaction (PPI) prediction identified potential interactors of GADD45G, and co-immunoprecipitation (co-IP) confirmed GADD45G interact with Cyclin-dependent kinase 1 (CDK1) and cyclin B1 (CCNB1). Several cell behavior assays were conducted in both in vitro and in vivo settings to comprehensively understand the impact of GADD45G dysregulation in EC.
Results: Our findings revealed a significant decrease in the expression of GADD45G in endometrial cancer tissues and cells, which was attributed to its methylation status. Reduced GADD45G expression correlated with increased invasive behaviors in EC cells. Furthermore, GADD45G negatively regulated CDK1 and CCNB1, promoting invasive behaviors at transcript and protein levels.
Conclusion: This study demonstrated that the downregulation of GADD45G, mediated by methylation, facilitates the invasive behaviors of EC cells through interaction with the CDK1/CCNB1. These findings enhance understanding of the molecular mechanisms underlying endometrial cancer and suggest potential therapeutic strategies targeting GADD45G for treatment.
(Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje