Giulia Poli1, Maria G Egidi2, Giovanni Cochetti3, Stefano Brancorsini1, Ettore Mearini2. 1. Department of Experimental Medicine, University of Perugia, Terni, Italy. 2. Department of Surgical and Biomedical Sciences, Clinic of Urology, University of Perugia, Perugia, Italy. 3. Department of Surgical and Biomedical Sciences, Clinic of Urology, University of Perugia, Perugia, Italy - giovannicochetti@libero.it.
Abstract
BACKGROUND: Exosomes are membrane vesicles secreted by both cancerous and normal cells which play important roles during intercellular communications and oncogenic transformation. Many reports highlight the importance of exosomal microRNAs (miRNAs) as pro-tumorigenic mediators during carcinogenesis, since they regulate all these pathways at the post-transcriptional level. Since bladder cancer cells have a high immunogenic potential, from one hand, and inflammation process is intimately connected to carcinogenesis, from the other, the interest in analyzing inflammasome-related exo-miRNAs is apparent. The modulation of miRNAs targeting NOD-like receptor mRNAs in patients harboring bladder cancer has been assessed in our previous studies. METHODS: In the present report, we characterized the previously selected miRNAs in the soluble fraction of the same bladder cancer patient cohort, stratified according to the risk of recurrence and progression. Exosome precipitation and isolation were performed; the expression levels of exosomal miRNAs were compared with their cellular counterparts. RESULTS: An up-regulation of exosomal miR-141-3p and miR-19a-3p with respect to urine sediment was reported. Linear regression analysis showed a significant negative correlation for the same miRNAs. Moreover, exosomal miRNAs increased in low risk compared to high risk patients, which was opposite to that observed for urine sediment. CONCLUSIONS: Our work demonstrated the inverse correlation between exosomal and cellular miRNAs in patients with bladder cancer. The fact that these miRNAs were higher in exosomal than cellular fraction allowed us to hypothesize their active compartmentalization during cancer progression, suggesting their potential role as cancer messengers.
BACKGROUND: Exosomes are membrane vesicles secreted by both cancerous and normal cells which play important roles during intercellular communications and oncogenic transformation. Many reports highlight the importance of exosomal microRNAs (miRNAs) as pro-tumorigenic mediators during carcinogenesis, since they regulate all these pathways at the post-transcriptional level. Since bladder cancer cells have a high immunogenic potential, from one hand, and inflammation process is intimately connected to carcinogenesis, from the other, the interest in analyzing inflammasome-related exo-miRNAs is apparent. The modulation of miRNAs targeting NOD-like receptor mRNAs in patients harboring bladder cancer has been assessed in our previous studies. METHODS: In the present report, we characterized the previously selected miRNAs in the soluble fraction of the same bladder cancerpatient cohort, stratified according to the risk of recurrence and progression. Exosome precipitation and isolation were performed; the expression levels of exosomal miRNAs were compared with their cellular counterparts. RESULTS: An up-regulation of exosomal miR-141-3p and miR-19a-3p with respect to urine sediment was reported. Linear regression analysis showed a significant negative correlation for the same miRNAs. Moreover, exosomal miRNAs increased in low risk compared to high risk patients, which was opposite to that observed for urine sediment. CONCLUSIONS: Our work demonstrated the inverse correlation between exosomal and cellular miRNAs in patients with bladder cancer. The fact that these miRNAs were higher in exosomal than cellular fraction allowed us to hypothesize their active compartmentalization during cancer progression, suggesting their potential role as cancer messengers.