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Updated: Aug 31, 2025

Author Spotlight: Impact of Intergenic Interactions on Disease-Identifying Dark Biomarkers
Published on: March 1, 2024
Pan-cancer analysis of mRNA stability for decoding tumour post-transcriptional programs
Gabrielle Perron1,2, Pouria Jandaghi2, Elham Moslemi2
1Department of Human Genetics, McGill University, Montreal, QC, H3A 1B1, Canada.
None:
Measuring mRNA decay in tumours is a prohibitive challenge, limiting our ability to map the post-transcriptional programs of cancer. Here, using a statistical framework to decouple transcriptional and post-transcriptional effects in RNA-seq data, we uncover the mRNA stability changes that accompany tumour development and progression. Analysis of 7760 samples across 18 cancer types suggests that mRNA stability changes are ~30% as frequent as transcriptional events, highlighting their widespread role in shaping the tumour transcriptome. Dysregulation of programs associated with >80 RNA-binding proteins (RBPs) and microRNAs (miRNAs) drive these changes, including multi-cancer inactivation of RBFOX and miR-29 families. Phenotypic activation or inhibition of RBFOX1 highlights its role in calcium signaling dysregulation, while modulation of miR-29 shows its impact on extracellular matrix organization and stemness genes. Overall, our study underlines the integral role of mRNA stability in shaping the cancer transcriptome, and provides a resource for systematic interrogation of cancer-associated stability pathways.
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