RNY4 in circulating exosomes of patients with pediatric Anaplastic Large Cell Lymphoma: an active player?

Emerging evidence indicates that extracellular vesicles, particularly exosomes, play a role in several biological processes and actively contribute to cancer development and progression, by carrying and delivering proteins, transcripts and small RNAs (sRNAs). We profiled by RNA-seq the sRNA content of circulating exosomes of 20 pediatric patients with Anaplastic Large Cell Lymphoma (ALCL), 5 healthy controls and of 5 ALCL cell lines. Our analysis disclosed that non-miRNA derived sRNAs constitute the prominent fraction of sRNA loaded in exosomes. A fragment of RNY4 was the most abundant of 180 sRNAs significantly enriched in exosomes of ALCL patients compared to controls. Further investigation by qRT-PCR of RNY4 fragments and full-length sequence disclosed that the latter is massively loaded into exosomes of ALCL patients with more advanced and aggressive disease. Since recent findings supported a role of RNY4 in the modulation of tumor microenvironment, our data open new possibilities to understand how tumor derived exosomes can facilitate disease spread in ALCL patients. Overall design: Tumor biopsies and plasmatic exosomes from ALCL pediatric patients; plasmatic exosomes from healthy donors; exosomes from ALCL cell lines culture surnatants.