Unknown

Dataset Information

0

DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts.


ABSTRACT: DNA-demethylating agents have shown clinical anti-tumor efficacy via an unknown mechanism of action. Using a combination of experimental and bioinformatics analyses in colorectal cancer cells, we demonstrate that low-dose 5-AZA-CdR targets colorectal cancer-initiating cells (CICs) by inducing viral mimicry. This is associated with induction of dsRNAs derived at least in part from endogenous retroviral elements, activation of the MDA5/MAVS RNA recognition pathway, and downstream activation of IRF7. Indeed, disruption of virus recognition pathways, by individually knocking down MDA5, MAVS, or IRF7, inhibits the ability of 5-AZA-CdR to target colorectal CICs and significantly decreases 5-AZA-CdR long-term growth effects. Moreover, transfection of dsRNA into CICs can mimic the effects of 5-AZA-CdR. Together, our results represent a major shift in understanding the anti-tumor mechanisms of DNA-demethylating agents and highlight the MDA5/MAVS/IRF7 pathway as a potentially druggable target against CICs.

SUBMITTER: Roulois D 

PROVIDER: S-EPMC4843502 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications


DNA-demethylating agents have shown clinical anti-tumor efficacy via an unknown mechanism of action. Using a combination of experimental and bioinformatics analyses in colorectal cancer cells, we demonstrate that low-dose 5-AZA-CdR targets colorectal cancer-initiating cells (CICs) by inducing viral mimicry. This is associated with induction of dsRNAs derived at least in part from endogenous retroviral elements, activation of the MDA5/MAVS RNA recognition pathway, and downstream activation of IRF  ...[more]

Similar Datasets

2015-08-27 | GSE62086 | GEO
2015-08-27 | E-GEOD-62086 | biostudies-arrayexpress
| S-EPMC3860592 | biostudies-literature
| S-EPMC5873356 | biostudies-literature
| S-EPMC9385881 | biostudies-literature
| S-EPMC7839369 | biostudies-literature
2022-04-29 | GSE134861 | GEO
| S-EPMC10349869 | biostudies-literature
| S-EPMC4036667 | biostudies-literature
| S-EPMC3871232 | biostudies-literature