METTL3 regulates breast cancer-associated alternative splicing switches

Alternative splicing (AS) enables the differential inclusion of exons from a given transcript, thereby contributing to the transcriptome and proteome diversity. Aberrant AS patterns play major roles in developing different pathologies, including breast cancer. N6-methyladenosine (m6A), the most abundant internal modification of eukaryotic mRNA, influences tumor progression and metastasis in breast cancer, and it has been recently linked to AS regulation. The study identifies a specific AS signature associated with breast tumorigenesis in vitro. Specifically, it was found that both m6A deposition at splice site boundaries and splicing and transcription factor transcripts, such as MYC, direct AS switches of specific breast cancer-associated transcripts. Finally, the findings show that five of the AS events validated in vitro are associated with a poor overall survival rate for patients with breast cancer, suggesting the use of these AS events as a novel potential prognostic biomarker.