Poli Giulia, Egidi Maria G, Cochetti Giovanni, Brancorsini Stefano, Mearini Ettore
Department of Experimental Medicine, University of Perugia, Terni, Italy.
Department of Surgical and Biomedical Sciences, Clinic of Urology, University of Perugia, Perugia, Italy.
Minerva Urol Nefrol. 2020 Apr;72(2):207-213. doi: 10.23736/S0393-2249.19.03297-1. Epub 2019 May 28.
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.
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.
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.
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.
外泌体是由癌细胞和正常细胞分泌的膜性囊泡，在细胞间通讯和致癌转化过程中发挥重要作用。许多报告强调了外泌体微小RNA（miRNA）在致癌过程中作为促肿瘤介质的重要性，因为它们在转录后水平上调节所有这些途径。一方面，膀胱癌细胞具有高免疫原性潜力；另一方面，炎症过程与致癌作用密切相关，因此分析炎性小体相关的外泌体miRNA具有明显的意义。在我们之前的研究中，已经评估了膀胱癌患者中靶向NOD样受体mRNA的miRNA的调节情况。
在本报告中，我们对同一膀胱癌患者队列的可溶性部分中先前选择的miRNA进行了表征，根据复发和进展风险进行分层。进行了外泌体沉淀和分离；将外泌体miRNA的表达水平与其细胞对应物进行了比较。
报告了外泌体miR-141-3p和miR-19a-3p相对于尿沉渣的上调。线性回归分析显示相同miRNA存在显著负相关。此外，与高风险患者相比，低风险患者的外泌体miRNA增加，这与尿沉渣中观察到的情况相反。
我们的工作证明了膀胱癌患者中外泌体miRNA与细胞miRNA之间的负相关。这些miRNA在外泌体中比细胞部分中更高这一事实使我们能够假设它们在癌症进展过程中的活跃分隔，表明它们作为癌症信使的潜在作用。
