Transcriptomics

Dataset Information

0

Epigenetic therapy induces transcription of Inverted SINEs and ADAR1 dependency


ABSTRACT: In this study we show that intronic and intergenic SINE elements, specifically inverted repeats (IR) Alus, are the major source of drug-induced immunogenic dsRNA. These IR-Alus are frequently located downstream of ‘orphan’ CpG Islands (CGIs). In mammals, the enzyme Adenosine Deaminases Acting on RNA (ADAR1) targets and destabilizes IR-Alu dsRNA, which prevents activation of MDA5. We found that ADAR1 establishes a negative feedback loop, restricting the viral mimicry response to epigenetic therapy. Depletion of ADAR1 in patient-derived cancer cells potentiates the efficacy of epigenetic therapy, restraining tumour growth and reducing cancer initiation. Thus, epigenetic therapies trigger viral mimicry by inducing a subset of IR-Alus, leading to an ADAR1 dependency. Our findings suggest that combining epigenetic therapies with ADAR1 inhibitors represents a promising new strategy for cancer treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145639 | GEO | 2020/10/20

REPOSITORIES: GEO

Dataset's files

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

Similar Datasets

2024-09-05 | GSE213249 | GEO
2024-09-05 | GSE213248 | GEO
| PRJNA607783 | ENA
2023-10-03 | GSE198386 | GEO
2024-03-26 | GSE216639 | GEO
2023-08-07 | GSE224677 | GEO
2014-12-19 | E-GEOD-62917 | biostudies-arrayexpress
2024-04-17 | GSE248036 | GEO
2024-06-22 | PXD035635 | Pride
2023-01-22 | GSE222487 | GEO