CD73 restrains mutant β-catenin oncogenic activity in endometrial carcinomas

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Abstract Missense mutations in exon 3 of CTNNB1 , the gene encoding β-catenin, are associated with poor outcomes endometrial carcinomas (EC). Clinically, mutation status has been difficult to use as a predictive biomarker β-catenin oncogenic activity is modified by other factors, and these determinants unknown. Here we reveal that CD73 restrains mutants, its loss associates recurrence. Using 7 patient-specific genetic deletion or ectopic expression CD73, show increases β-catenin-TCF/LEF transcriptional activity. In cells lacking membrane levels mutant decreased which corresponded increased nuclear chromatin-bound β-catenin. These results suggest sequesters limit Adenosine A1 receptor phenocopied seen NT5E deletion, suggesting effect on mediated via attenuation adenosine signaling. RNA-seq analyses revealed alone drives pro-tumor Wnt/β-catenin and, loss, mutants dysregulate zinc-finger non-coding RNA expression. We identify novel regulator help explain variability patient EC. Graphical

Language: Английский

Effect of CpG Site -123 Methylation in HOTAIR Promoter on DNMT3A Binding and Transcriptional Silencing in Endometrial Cancer

International Journal of Newgen Research in Pharmacy & Healthcare, Journal Year: 2024, Volume and Issue: unknown, P. 193 - 195

Published: Dec. 31, 2024

Endometrial cancer is a common malignancy with significant epigenetic alterations, particularly involving DNA methylation. The long non-coding RNA HOTAIR regulates gene expression through mechanisms. This review investigates the specific impact of methylation at CpG site -123 within promoter region on DNMT3A binding and effects transcriptional silencing. Understanding these interactions provides insights into HOTAIR’s regulation highlights potential therapeutic targets for endometrial cancer.

Language: Английский