Breast cancer RNA carries an overlooked chemical mark, most common in the hardest-to-treat subtype

What is it about?

DNA carries chemical marks that help control which genes are switched on or off. Scientists have long studied one such mark, called 5-hydroxymethylcytosine, on DNA inside the cell's nucleus and found it is often reduced in cancer. In this study, we discovered that this same chemical mark also appears on RNA, the molecule cells use to carry out DNA's instructions, and that it sits in the cytoplasm, outside the nucleus. We found this cytoplasmic mark is more abundant in breast cancer tissue than in healthy tissue, especially in triple-negative breast cancer, one of the hardest subtypes to treat. We also found it linked to a protein called TET3. These findings suggest a previously unrecognised layer of chemical regulation that could eventually help identify or treat aggressive breast cancers.

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Photo by National Cancer Institute on Unsplash

Photo by National Cancer Institute on Unsplash

Why is it important?

We show that 5-hydroxymethylcytosine, a chemical mark traditionally studied on DNA, is also present on RNA in the cytoplasm of breast cancer cells, and is enriched in tumour tissue compared with healthy tissue. This challenges the long-standing view that this mark is simply lost in cancer, and instead reveals a previously overlooked regulatory layer specific to RNA. Two significant findings are that: a) cytoplasmic enrichment of this mark is most pronounced in triple-negative breast cancer, one of the most aggressive and hardest-to-treat subtypes, and b) it is linked to TET3, a protein not previously associated with RNA-based regulation in this disease, pointing to a new candidate mechanism and potential biomarker.

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