Work

Intragenic DNA methylation and BORIS-mediated cancer-specific splicing contribute to the Warburg effect

Year: 2017

Type: article

Abstract: Significance Recent advances in cancer epigenetics have shown the involvement of epigenetic abnormalities in the initiation and progression of cancer, but their role in cancer-specific aberrant splicing is not clear. The identification of upstream epigenetic regulators of cancer-specific splicing will enable us to therapeutically target aberrant splicing and provide an approach to cancer therapy. Here we have demonstrated a mechanism of intragenic DNA methylation-mediated regulation of alternative splicing by Brother of Regulator of Imprinted Sites (BORIS), which can contribute to breast cancer tumorigenesis by favoring the Warburg effect. The reversal of the Warburg effect was achieved by the inhibition of DNA methylation or down-regulation of BORIS, which may serve as a useful approach to inhibit the growth of breast cancer cells.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1708447114