Exosomes mediate cell-cell crosstalk in cancer progression by transferring a variety of biomolecules, including long noncoding RNAs (lncRNAs). Long non-coding RNA urothelial carcinoma-associated (UCA1) is a well-known lncRNA associated with the development and progression of various cancers, including colorectal cancer (CRC). However, the presence of UCA1 in exosomes and the roles and clinical values of exosomal UCA1 in CRC remain unknown. In this study, we systematically analyzed the expression profiles of exosomal lncRNAs in CRC patients using a high-throughput microarray assay. Then, we evaluated the UCA1 expression levels in a series of CRC tissues and the serum exosomes of CRC patients using quantitative real-time PCR. The roles of UCA1 on CRC in vitro and in vivo were investigated by MTT, colony formation, Transwell, quantitative real-time PCR, flow cytometry, and western blotting. The miRNA binding sites of UCA1 were predicted using the miRcode online database, and miR-143 was validated to target UCA1 by dual-luciferase activity assay and AGO2 RNA immunoprecipitation. Finally, the role of exosome-mediated UCA1 was further investigated by co-culturing with CRC cells. This study showed that UCA1 was upregulated in CRC tissues and functioned as an oncogene in CRC. Loss-of-function investigations showed that inhibition of UCA1 suppressed CRC cell proliferation and metastasis in vivo and in vitro. Mechanistically, UCA1 was identified as a miR-143 sponge. We also found that MYO6 was a direct target of miR-1205, which functioned as an oncogene in CRC. Moreover, UCA was also upregulated in the serum exosomes of CRC patients and could transfer UCA1 to CRC cells to increase their abilities of cell proliferation and migration. In conclusion, these data suggest that UCA1 could be an oncogene for CRC and may serve as a candidate target for new therapies in human CRC.

外来体通过转移多种生物分子（包括长的非编码RNA（lncRNA））来介导癌症进程中的细胞间串扰。长的非编码RNA泌尿道上皮癌相关基因（UCA1）是众所周知的lncRNA，与各种癌症，包括结直肠癌（CRC）的发生和发展有关。然而，外泌体中UCA1的存在以及外泌体UCA1在CRC中的作用和临床价值仍然未知。在这项研究中，我们使用高通量微阵列分析系统地分析了CRC患者外泌体lncRNA的表达谱。然后，我们使用定量实时PCR评估了一系列CRC组织和CRC患者血清外泌体中UCA1的表达水平。UCA1对CRC的角色，在体外和体内通过MTT，集落形成，Transwell，实时定量PCR，流式细胞仪和western blotting进行了研究。使用miRcode在线数据库预测了UCA1的miRNA结合位点，并通过双荧光素酶活性测定和AGO2 RNA免疫沉淀验证了miR-143靶向UCA1。最后，通过与CRC细胞共培养，进一步研究了外来体介导的UCA1的作用。这项研究表明，UCA1在CRC组织中上调，并在CRC中起癌基因的作用。功能丧失研究表明，抑制UCA1可抑制CRC细胞在体内和体外的增殖和转移。从机理上讲，UCA1被鉴定为miR-143海绵。我们还发现MYO6是miR-1205的直接靶标，而miR-1205在CRC中起癌基因的作用。此外，UCA在CRC患者的血清外泌体中也上调，并且可以将UCA1转移至CRC细胞，以增加其细胞增殖和迁移的能力。总之，这些数据表明UCA1可能是CRC的致癌基因，并且可以作为人类CRC新疗法的候选靶标。