An InDel Genomic Variant within a Bifunctional Super-Enhancer for LINC00636 and CD47 Regulation in Breast Cancer.

ABSTRACT: Highly accessible genomic super-enhancers often drive tumor-promoting programs, yet the impact of genomic variation within these regulatory elements remains unclear. Here, we identified a bifunctional super-enhancer that regulates the expression of cancer-promoting genes LINC00636 and CD47 in breast cancer. We discovered that a common germline insertion variant within the super-enhancer is associated with reduced chromatin accessibility at the super-enhancer locus. Deletion of the insertion in breast cancer cells increased chromatin accessibility, leading to upregulation of LINC00636 and CD47, enhanced resistance to nutrient-deprivation-induced apoptosis (mediated by CD47), activation of senescence (driven by elevated LINC00636), delayed cell death, and reduced infiltration of CD80^+</

SUBMITTER: Di Benedetto C 

PROVIDER: S-EPMC12637730 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature