Canonical and non-canonical miRNA degradation shapes state transitions and stemness in breast cancer

ABSTRACT: Target-directed microRNA degradation (TDMD) is an emerging post-transcriptional mechanism that controls miRNA turnover, yet its role in human cancers remains largely unexplored. Here, we combine CRISPRi-mediated ZSWIM8 depletion, miRNA-seq, and AGO2-eCLIP to define the TDMD landscape across breast cancer subtypes. We identify 19 high-confidence TDMD substrates, including miR-29b-3p and miR-33a/b-5p, and show that TDMD shapes miRNA target occupancy and target repression. Integration with single-cell transcriptomics reveals that TDMD of miR-29b-3p triggered by recruiting factor NREP transcript is associated with transcriptional plasticity along the epithelial-mesenchymal axis and marks a stem-like subpopulation of malignat cells with tumor-initiating potential in triple-negative breast cance

SUBMITTER: Carmela Rubolino 

PROVIDER: S-SCDT-10_1038-S44318-026-00889-8 | biostudies-other |

REPOSITORIES: biostudies-other