A concurrent canonical and modified miRNAome pan-cancer study on TCGA and TARGET cohorts leads to an enhanced resolution in cancer

Despite miRNA editing and shifted miRNA isoforms are gaining attention due to recent improvements in next-generation sequencing, a simultaneous study of both modifications in cancer is still missing. Here, we concurrently profiled miRNA editing and shifted miRNA isoforms in >13K miRNA-Seq samples across 38 cancer cohorts from The Cancer Genome Atlas and The Therapeutically Applicable Research to Generate Effective Treatments datasets. We investigated the differences among canonical miRNAs and a wider comprehensive miRNAome in terms of expression, clustering, dysregulation, and prognostic standpoint. We experimentally validated unique targeting for a shifted and edited miRNA isoform. Our findings outlined once more the importance of going beyond the well-established paradigm of one-mature-miRNA per miRNA arm to elucidate novel mechanisms related to cancer progression.