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| Status |
Public on Oct 01, 2021 |
| Title |
Transposon-triggered innate immune response confers cancer resistance to the blind mole rat [array] |
| Platform organisms |
Homo sapiens; Mus musculus; Rattus norvegicus |
| Sample organisms |
Mus musculus; Nannospalax ehrenbergi |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Blind mole rats (BMRs) are small rodents, characterized by exceptionally long lifespan (> 21 years) and resistance to both spontaneous and induced tumorigenesis. Here we report that cancer resistance in the BMR is mediated by retrotransposable elements (RTEs). BMR cells and tissues express very low levels of DNA methyltransferase 1 (DNMT1). Upon cell hyperplasia, the BMR genome DNA loses methylation, resulting in activation of RTEs. Up-regulated RTEs form cytoplasmic RNA/DNA hybrids, which activate cGAS-STING pathway to induce cell death. Although this mechanism is enhanced in the BMR, we show that it functions in mice and human. We propose that RTEs were coopted to serve as tumor suppressors that monitor cell proliferation and are activated in premalignant cells to trigger cell death via activation of innate immune response. RTEs activation is a double-edged sword, serving as a tumor suppressor but in late life contributing to aging via induction of sterile inflammation.
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| Overall design |
Using a custom Illumina chip HorvathMammalMethylChip40, we compared methylation of 37K conserved CpG sites between blind mole rat and mouse fibrolasts for both young and overproliferated cells. Five cell lines from each species were used for paired comparison.
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| Contributor(s) |
Horvath S, Zhao Y, Gorbunova V |
| Citation(s) |
34556881 |
| |
| Submission date |
Aug 09, 2021 |
| Last update date |
Dec 31, 2021 |
| Contact name |
Yang Zhao |
| E-mail(s) |
yangzhao926@outlook.com
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| Organization name |
University of Rochester
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| Department |
Biology
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| Street address |
60 Crittenden Blvd, Apt1240
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| City |
Rochester |
| State/province |
NY |
| ZIP/Postal code |
14620 |
| Country |
USA |
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| Platforms (1) |
| GPL28271 |
Illumina HorvathMammalianMethylChip40 BeadChip |
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| Samples (20)
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| This SubSeries is part of SuperSeries: |
| GSE181733 |
Transposon-triggered innate immune response confers cancer resistance to the blind mole rat |
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| Relations |
| BioProject |
PRJNA753124 |
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