The miRNA content of circulating exosomes in DLBCL patients and in vitro influence of DLBCL-derived exosomes on miRNA expression of healthy B-cells from peripheral blood

Article type: Research Article

Authors: Caner, Vildan^{a; 1; *} | Cetin, Gokhan Ozan^{a; 1} | Hacioglu, Sibel^b | Baris, Ikbal Cansu^c | Tepeli, Emre^{a; **} | Turk, Nilay Sen^d | Bagci, Gulseren^a | Yararbas, Kanay^{e; ***} | Cagliyan, Gulsum^b

Affiliations: [a] Department of Medical Genetics, School of Medicine, Pamukkale University, Denizli, Turkey | [b] Department of Hematology, School of Medicine, Pamukkale University, Denizli, Turkey | [c] Department of Medical Biology, School of Medicine, Pamukkale University, Denizli, Turkey | [d] Department of Medical Pathology, School of Medicine, Pamukkale University, Denizli, Turkey | [e] Department of Medical Genetics, School of Medicine, Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey

Correspondence: [*] Corresponding author: Vildan Caner, Pamukkale University, School of Medicine, Department of Medical Genetics, Denizli, Turkey. Tel.: +90 258 296 1691, Fax: +90 258 296 1765, E-mail: vcaner@pau.edu.tr.

Correspondence: [**] Current address: Next Genetic Center, Istanbul, Turkey.

Correspondence: [***] Current address: Department of Medical Genetics, School of Medicine, Demiroglu Bilim University, Istanbul, Turkey.

Note: [1] The authors contributed equally to the work.

Abstract: BACKGROUND: Due to the heterogeneous nature of Diffuse Large B-cell Lymphoma (DLBCL), the mechanisms underlying tumor development and progression have not yet been fully elucidated. OBJECTIVE: This study aimed to compare the characteristics of plasma exosomes of DLBCL patients and healthy individuals and to evaluate the exosomal interactions between DLBCL cell lines and normal B-cells. METHODS: Exosome isolation was performed using an ultracentrifugation-based protocol from plasma of 20 patients with DLBCL and 20 controls. The expression of miRNAs from exosome samples was analyzed using a miRNA expression microarray. The presence of exosome-mediated communication between the lymphoma cells and normal B-cells was determined by the co-culture model. RESULTS: A significant increase in plasma exosome concentrations of DLBCL patients was observed. There was also a significant decrease in the expression of 33 miRNAs in plasma exosomes of DLBCL patients. It was determined that normal B-cells internalize DLBCL-derived exosomes and then miRNA expression differences observed in normal B-cells are specific to lymphoma-subtypes. CONCLUSIONS: MiR-3960, miR-6089 and miR-939-5p can be used as the miRNA signature in DLBCL diagnosis. We suppose that the exosomes changed the molecular signature of the target cells depending on the genomic characterization of the lymphoma cells they have originated.

Keywords: Diffuse large B-cell lymphoma, exosomes, miRNA, B-cells, cellular uptake

DOI: 10.3233/CBM-210110

Journal: Cancer Biomarkers, vol. 32, no. 4, pp. 519-529, 2021