Abstract
Background aims
Epigenetic silencing of tumor suppressor genes by aberrant DNA methylation and histone
modifications at their promoter regions plays an important role in the initiation
and progression of cancer. The therapeutic effect of the widely used epigenetic drugs,
including DNA methyltransferase inhibitors and histone deacetylase inhibitors, remains
unsatisfactory. One important underlying factor in the ineffectiveness of these drugs
is that their actions lack specificity.
Methods
To investigate whether oocyte extract can be used for epigenetic re-programming of
cancer cells, H460 human lung cancer cells were reversibly permeabilized and incubated
with bovine oocyte extract.
Results
Bisulfite sequencing showed that bovine oocyte extract induced significant demethylation
at hypermethylated promoter CpG islands of the tumor suppressor genes RUNX3 and CDH1; however, the DNA methylation levels of repetitive sequences were not affected. Chromatin
immunoprecipitation showed that bovine oocyte extract significantly reduced transcriptionally
repressive histone modifications and increased transcriptionally activating histone
modifications at the promoter regions of RUNX3 and CDH1. Bovine oocyte extract reactivated the expression of RUNX3 and CDH1 at both the messenger RNA and the protein levels without up-regulating the transcription
of pluripotency-associated genes. At the functional level, anchorage-independent proliferation,
migration and invasion of H460 cells was strongly inhibited.
Conclusions
These results demonstrate that bovine oocyte extract reactivates epigenetically silenced
tumor suppressor genes by remodeling the epigenetic modifications at their promoter
regions. Bovine oocyte extract may provide a useful tool for investigating epigenetic
mechanisms in cancer and a valuable source for developing novel safe therapeutic approaches
that target epigenetic alterations.
Key Words
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Article info
Publication history
Published online: June 24, 2013
Accepted:
May 5,
2013
Received:
March 10,
2013
Identification
Copyright
© 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
