Research led by the Kafasla lab reveals that alternative splicing (AS) deregulation in Pancreatic Neuroendocrine Tumors results in neuronal phenotype and disrupted hormone secretion.
In this study, SRRM3 neuronal splicing factor is found upregulated in pancreatic neuroendocrine tumours (PanNETs), driving the inclusion of a distinct set of neuronal microexons in the mRNAs. These microexons reshape secretory vesicle dynamics and trafficking, contributing to an aberrant neuronal-like identity in PanNET cells. By using knock-down models for SRRM3 (with si or shRNA) or targeting the inclusion of key microexons (with splice-switching oligonucleotides), tumour characteristics were reversed in both cellular and animal models. These findings establish a novel link between splicing deregulation and secretory dysfunction in PanNETs, highlighting new opportunities for therapeutic intervention.
Reference:
Myrto Potiri, Charikleia Moschou, Zoi Erpapazoglou, Georgia Rouni, Anastasia Kotsoni, Margarita Andreadou, Anastasios Klavdianos, Melina Dragolia, Vasileios Ntafis, Joerg Schrader, Jonas Juan-Mateu, Skarlatos G. Dedos, Martina Samiotaki, Vassiliki Kostourou, Malgorzata E. Rogalska, Panagiota Kafasla
Cell Reports, DOI: 10.1016/j.celrep.2025.116022