Transcriptomics

Dataset Information

0

XRN1 deletion induces PKR-dependent cell lethality in interferon-activated cancer cells


ABSTRACT: Emerging data suggest that induction of viral mimicry responses through activation of double-stranded RNA (dsRNA) sensors in cancer cells is a promising therapeutic strategy. One approach to induce viral mimicry is to target molecular regulators of dsRNA sensing pathways. Here, we show that the exoribonuclease XRN1 is a negative regulator of the dsRNA sensor protein kinase R (PKR) in cancer cells with high interferon-stimulated gene (ISG) expression. XRN1 deletion causes PKR pathway activation and consequent cancer cell lethality. Disruption of interferon signaling with the JAK1/2 inhibitor ruxolitinib can decrease cellular PKR levels and rescue sensitivity to XRN1 deletion. Conversely, interferon-b stimulation can increase PKR levels and induce sensitivity to XRN1 inactivation. Lastly, XRN1 deletion causes accumulation of endogenous complementary sense/anti-sense RNAs, which may represent candidate PKR ligands. Our data demonstrate how XRN1 regulates PKR, and how this interaction creates a vulnerability in cancer cells with an activated interferon cell state.

ORGANISM(S): Homo sapiens

PROVIDER: GSE248036 | GEO | 2024/04/17

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

| PRJNA1041442 | ENA
2023-10-03 | GSE198386 | GEO
2013-12-27 | E-GEOD-46959 | biostudies-arrayexpress
2024-06-16 | GSE269684 | GEO
2013-12-27 | GSE46959 | GEO
2021-05-10 | PXD022564 | Pride
2021-12-23 | GSE183941 | GEO
2004-01-30 | E-MEXP-50 | biostudies-arrayexpress
| PRJNA1123226 | ENA
2023-02-21 | GSE199744 | GEO