ARID1A Governs Genomic Stability and Proliferation in SCLC via c-MYC/PARP1 Suppression Driving Vulnerability to BET Inhibitors.

ABSTRACT: Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor among the most lethal cancers. ARID1A has a dual role in oncogenic and tumor-suppressive functions, depending on the type of cancer. However, its role in SCLC remains unclear. Herein, we showed that ARID1A was highly expressed and correlated with prognosis in SCLC. In vitro and in vivo investigations manifested that ARID1A inhibited cell survival, proliferation, and tumor growth, functioning as a gatekeeper for cell proliferation and a caretaker of genome stability in SCLC cells. Mechanistically, ARID1A transcriptionally represses c-MYC and PARP1 expression. ARID1A depletion triggered replication stress response (RSR), DNA double-strand breaks (DSBs), and PI3K/AKT pathway activation, which could

SUBMITTER: Cao G 

PROVIDER: S-EPMC12489181 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature