Medical Xpress / The Wistar Institute / mBio ^ | Aug. 22, 2023 | Sarah Preston-Alp et al
In the paper, Wistar's Tempera lab investigates the epigenetic characteristics of gastric cancer associated with the Epstein-Barr Virus: EBVaGC.
Italo Tempera, Ph.D. and collaborators demonstrate that an epigenetically active compound called decitabine disrupts the genome of EBVaGC by epigenetically modifying the cancer's DNA. "What we have identified is essentially a self-destruct button within this kind of cancer, and our paper shows that we figured out how to press that self-destruct button," said Tempera. "Normally, a latent virus that reactivates and starts to kill cells is a bad thing. But by switching that viral lytic process back on in these cancer cells by using epigenetic signaling, we're effectively getting the virus to kill the cancer cells that it's responsible for in the first place."
In EBVaGC, the cancer cells' DNA is hypermethylated. As a silencer of gene expression, DNA methylation allows EBV to remain latent. This methylation pattern plays a significant role in regulating the EBV latency-lysis cycle within the cancer cells.
DNA methylation, as an epigenetic factor, usually functions as a gene-silencing mechanism, but methylation can prevent the protein the gene encodes from being transcribed.
To disrupt this epigenetic profile, the researchers turned to decitabine, a compound known for its ability to reduce DNA methylation levels (i.e., to hypomethylate DNA). Tempera and his co-authors treated two cell lines that were derived from EBVaGC tumors with decitabine. The cell lines that received the treatment demonstrated massive reductions in DNA methylation across the genome relative to the control.
In observing the effects of decitabine treatment on EBVaGC, Tempera's team found a significant disruption of the cancer's epigenetic profile. The EBV genome within EBVaGC treated with decitabine resulted in widespread, mostly uniform hypomethylation of the EBVaGC epigenome (with few exceptions).
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