Maggisano Valentina, Capriglione Francesca, Verrienti Antonella, Celano Marilena, Gagliardi Agnese, Bulotta Stefania, Sponziello Marialuisa, Mio Catia, Pecce Valeria, Durante Cosimo, Damante Giuseppe, Russo Diego
Department of Health Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.
Department of Translational and Precision Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Biomedicines. 2022 Apr 21;10(5):961. doi: 10.3390/biomedicines10050961.
The release of molecules in exosomal cargoes is involved in tumor development and progression. We compared the profiles of exosomal microRNAs released by two thyroid cancer cell lines (TPC-1 and K1) with that of non-tumorigenic thyroid cells (Nthy-ori-3-1), and we explored the network of miRNA-target interaction. After extraction and characterization of exosomes, expression levels of microRNAs were investigated using custom TaqMan Advanced array cards, and compared with those expressed in the total cell extracts. The functional enrichment and network-based analysis of the miRNAs' targets was also performed. Five microRNAs (miR-21-5p, miR-31-5p, miR-221-3p, miR-222-3p, and let-7i-3p) were significantly deregulated in the exosomes of tumor cells vs. non-tumorigenic cells, and three of them (miR-31-5p, miR-222-3p, and let-7i-3p) in the more aggressive K1 compared to TPC-1 cells. The network analysis of the five miRNAs identified some genes as targets of more than one miRNAs. These findings permitted the identification of exosomal microRNAs secreted by aggressive PTC cells, and indicated that their main targets are regulators of the tumor microenvironment. A deeper analysis of the functional role of the targets of exosomal miRNAs will provide further information on novel targets of molecular treatments for these neoplasms.
外泌体货物中分子的释放参与肿瘤的发生和发展。我们比较了两种甲状腺癌细胞系（TPC-1和K1）与非致瘤性甲状腺细胞（Nthy-ori-3-1）释放的外泌体微小RNA谱，并探索了miRNA-靶标相互作用网络。在提取和鉴定外泌体后，使用定制的TaqMan Advanced阵列卡研究微小RNA的表达水平，并与全细胞提取物中表达的水平进行比较。还对miRNA靶标进行了功能富集和基于网络的分析。与非致瘤性细胞相比，肿瘤细胞外泌体中有5种微小RNA（miR-21-5p、miR-31-5p、miR-221-3p、miR-222-3p和let-7i-3p）显著失调，其中3种（miR-31-5p、miR-222-3p和let-7i-3p）在侵袭性更强的K1细胞中与TPC-1细胞相比失调更明显。对这5种微小RNA的网络分析确定了一些基因是不止一种微小RNA的靶标。这些发现有助于鉴定侵袭性乳头状甲状腺癌细胞分泌的外泌体微小RNA，并表明它们的主要靶标是肿瘤微环境的调节因子。对外泌体微小RNA靶标的功能作用进行更深入分析将为这些肿瘤分子治疗的新靶标提供更多信息。
