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Meropi Plousiou,1 Alessandro De Vita,2 Giacomo Miserocchi,2 Erika Bandini,1 Ivan Vannini,1 Mattia Melloni,1 Nestory Masalu,3 Francesco Fabbri,1 Patrizia Serra4 1Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy; 2Osteoncology Unit, Bioscience Laboratory IRCCS Istituto Romagnolo Per lo Studio dei Tumori (IRST), “Dino Amadori”, 47014 Meldola, Italy; 3Unit of Biostatistics and Clinical Trials, Bioscience Laboratory IRCCS Istituto Romagnolo Per lo Studio dei Tumori (IRST), “Dino Amadori”, 47014 Meldola, Italy; 4Unit of Biostatistics and Clinical Trials, IRCCS Istituto Scientifico Romagnolo Per lo Studio dei Tumori (IRST), “Dino Amadori”, Meldola, ItalyCorrespondence: Meropi Plousiou, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy, Tel +39 0543739298, Fax +39 0543739221, Email meropi.plousiou@irst.emr.itIntroduction: Retinoblastoma (Rb) is the most common ocular paediatric malignancy and is caused by a mutation of the two alleles of the tumor suppressor gene, RB1. The tumor microenvironment (TME) represents a complex system whose function is not yet well defined and where microvesicles, such as exosomes, play a key role in intercellular communication. Micro-RNAs (mRNAs) have emerged as important modifiers of biological mechanisms involved in cancer and been able to regulate tumor progression.Methods: Co-culture of monocytes with retinoblastoma cell lines, showed a significant growth decrease. Given the interaction between Rb cells and monocytes, we investigated the role of the supernatant in the cross-talk between cell lines, by taking the product of the co-culture and then using it as a culture medium for Rb cells.Results: miR-142-3p showed to be particularly over-expressed both in the Rb cell line and in the medium used for their culture, comparing to control cell line and the normal supernatant, respectively. Therefore, we provided evidence that miR-142-3p is released by monocytes in the co-culture medium’s exosomes and that it is subsequently up-taken by Rb cells, causing the inhibition of proliferation of Rb cell line by affecting cell cycle progression.Conclusion: This study highlights the role of exosomic miR-142-3p in the TME of Rb and identifies new molecular targets, which are able to control tumor growth aiming the development of a forward-looking miR-based strategy.Keywords: tumor microenvironment, microvescicles, microRNAs, co-culture, monocytes, cross-talk