RNY4 in Circulating Exosomes of Patients With Pediatric Anaplastic Large Cell Lymphoma: An Active Player?

Federica Lovisa; Piero Di Battista; Enrico Gaffo; Carlotta C Damanti; Anna Garbin; Ilaria Gallingani; Elisa Carraro; Marta Pillon; Alessandra Biffi; Stefania Bortoluzzi; Lara Mussolin

doi:10.3389/fonc.2020.00238

RNY4 in Circulating Exosomes of Patients With Pediatric Anaplastic Large Cell Lymphoma: An Active Player?

Front Oncol. 2020 Feb 27:10:238. doi: 10.3389/fonc.2020.00238. eCollection 2020.

Authors

Federica Lovisa^{1

2}, Piero Di Battista^{1

2}, Enrico Gaffo³, Carlotta C Damanti^{1

2}, Anna Garbin^{1

2}, Ilaria Gallingani^{1

2}, Elisa Carraro¹, Marta Pillon¹, Alessandra Biffi^{1

2

4}, Stefania Bortoluzzi^{3

5}, Lara Mussolin^{1

2}

Affiliations

¹ Clinic of Pediatric Onco-Hematology, Department of Women's and Children's Health, University of Padova, Padova, Italy.
² Istituto di Ricerca Pediatrica Città della Speranza, Padova, Italy.
³ Department of Molecular Medicine, University of Padova, Padova, Italy.
⁴ Gene Therapy Program, Dana Farber/Boston Children's Cancer and Blood Disorders Centers, Boston, MA, United States.
⁵ CRIBI Interdepartmental Research Center for Innovative Biotechnologies (CRIBI), University of Padova, Padova, Italy.

Abstract

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). There is high interest in studying exosomes of cancer patients both to develop non-invasive liquid biopsy tests for risk stratification and to elucidate their possible involvement in disease mechanisms. We profiled by RNA-seq the sRNA content of circulating exosomes of 20 pediatric patients with Anaplastic Large Cell Lymphoma (ALCL) and five healthy controls. Our analysis disclosed that non-miRNA derived sRNAs constitute the prominent fraction of sRNA loaded in exosomes and identified 180 sRNAs significantly more abundant in exosomes of ALCL patients compared to controls. YRNA fragments, accounting for most of exosomal content and being significantly increased in ALCL patients, were prioritized for further investigation by qRT-PCR. Quantification of RNY4 fragments and full-length sequences disclosed that the latter are massively loaded into exosomes of ALCL patients with more advanced and aggressive disease. These results are discussed in light of recent findings on the role of RNY4 in the modulation of tumor microenvironment.

Keywords: ALCL; RNA-seq; YRNA; exosomes; liquidbiopsy; small RNA.