ANP32A-mediated histone 3 K27 acetylation is essential for sotorasib activity in KRAS-mutant non-small cell lung cancer.

ABSTRACT: Drug resistance is a major challenge for the target therapy of KRAS-mutant non-small cell lung cancer (NSCLC). Here, we observe that ANP32A is tightly associated with KRAS-mutant NSCLC and serves as an unfavorable prognosis factor. ANP32A deficiency impaired cell proliferation, migration, invasion, and cell cycle progression and induced sotorasib (Sot) resistance in KRAS-mutant NSCLC cells, which were reversed by ANP32A reoverexpression in ANP32A-deficient cells. Mechanistically, ANP32A deficiency impaired histone 3 acetylation at lysine 27 (H3K27Ac). Particularly, ANP32A deficiency reduced H3K27Ac of the YEATS4 gene promoter and downregulated YEATS4 expression. ANP32A also interacted with YEATS4 and promoted its binding to H3K27Ac. Furthermore, YEATS4 overexpression partially restored ANP

SUBMITTER: Pan K 

PROVIDER: S-EPMC12857290 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature