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Effect of depletion of ISG20 on gene expression in EMT6 mouse breast cancer cells with RNA-Seq.

ABSTRACT: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the highest rates of recurrence, metastasis and patient mortality due to lack of effective targeted therapies. In this study, we demonstrate that ISG20 expression is induced by hypoxia and directly targeted by HIF-1 for transcription in TNBC cells. ISG20 functions as RNA exonuclease to target mRNAs for degradation, resulting in breast cancer stem cell specification and lung metastasis, and also cancer cell immune evasion. Mostly importantly, ISG20 silencing could markedly increase the sensitivity of TNBC to anti-PD1 immune checkpoint blockade (ICB) in a mouse model. Our data suggested that, in combination with immunotherapy, targeting ISG20 might be an effective strategy for TNBC treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE287164 | GEO | 2025/11/25

REPOSITORIES: GEO

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Effect of ISG20 expression (wild-type or M1 mutant) on total RNA expression.

Project description:ISG20 is an interferon-induced 3'-to-5' RNA exonuclease that acts as a broad antiviral innate defense factor. At present, the features that expose RNA to the action of ISG20 remain unclear. However recent studies have pinpointed to RNA epitranscriptomic modifications as modulators that either expose or protect viral RNAs from ISG20, raising the question as to how cellular RNAs, on which these modifications are abundant, cope with ISG20. To obtain an unbiased perspective on this issue, we used RNAseq to pinpoint to the RNA elements that regulate the balance between susceptibility and resistance to ISG20.

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