DOT1L inhibition exerts the anti-tumor effect by activating interferon signaling in breast cancer cells.

ABSTRACT:

Background

DOT1L, a histone H3 lysine 79 (H3K79) methyltransferase, is a potential therapeutic target in various malignancies. In the present study, we aimed to clarify the anti-tumor effect of DOT1L inhibition in breast cancer.

Methods

Estrogen receptor (ER)-positive/HER2-negative breast cancer cells (MCF7) and ER-negative/HER2-positive cells (SKBR3) were treated with a DOT1L inhibitor (SGC0946, EPZ-5676), after which colony formation assays, cell cycle assays, flow cytometry, gene expression microarray analysis, chromatin immunoprecipitation sequencing (ChIP-seq) and single-cell Assay for Transposase-Accessible Chromatin sequencing (scATAC-seq) were performed. Genetic ablation of STING was performed using the CRISPR/Cas9 system.

Results

Treatment with a DOT1L inhibi

SUBMITTER: Yoshido A 

PROVIDER: S-EPMC12659069 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature