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DOT1L inhibition exerts anti-tumor effects through activating interferon signaling in breast cancer cells

ABSTRACT: DOT1L, a histone H3 lysine 79 (H3K79) methyltransferase, is a potential therapeutic target in various malignancies. In the current study, we aimed to clarify the antitumor effect of DOT1L inhibition in breast cancer. Treatment with DOT1L inhibitors (SGC0942, EPZ-5676) suppressed proliferation and induced cell cycle arrest and apoptosis in estrogen receptor (ER)-positive/HER2-negative cancer cells (MCF7) as well as in ER-negative/HER2-positive cancer cells (SKBR3). Transcriptome and epigenome analysis revealed that DOT1L inhibition activated transcription of a number of interferon (IFN)-related genes (IRGs) in both cell lines. Our data suggest that the anti-breast cancer cell effect of DOT1L inhibition is mediated multiple mechanisms including activation of innate immune signaling.

ORGANISM(S): Homo sapiens

PROVIDER: GSE286942 | GEO | 2025/11/28

REPOSITORIES: GEO

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