Multidimensional OMICs reveal ARID1A orchestrated control of DNA damage, splicing, and cell cycle in normal-like and malignant urothelial cells.

ABSTRACT: Epigenetic regulators, such as the SWI/SNF complex, with important roles in tissue development and homeostasis, are frequently mutated in cancer. ARID1A, a subunit of the SWI/SNF complex, is mutated in approximately 20% of all bladder tumors; however, the consequences of this remain poorly understood. Finding truncations to be the most common mutation, we generated loss- and gain-of-function models to conduct RNA-Seq, interactome analyses, Omni-ATAC-Seq, and functional studies to characterize ARID1A-affected pathways potentially suitable for the treatment of ARID1A-deficient bladder cancers. We observed decreased cell proliferation and deregulation of stress-regulated pathways, including DNA repair, in ARID1A-deficient cells. Furthermore, ARID1A was linked to alternative splicing and trans

SUBMITTER: Schlosser RM 

PROVIDER: S-EPMC12688176 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature