Department of Three Wards of Department of Gynecology Oncology, Shaanxi Provincial Cancer Hospital , Xi'an, Shaanxi, China.
Department of Gynecology, Baoji Maternal and Children Health Care Hospital , Baoji, Shaanxi, China.
Cancer Biol Ther. 2020 Aug 2;21(8):717-725. doi: 10.1080/15384047.2020.1764318. Epub 2020 May 20.
Emerging evidence had highlighted that exosomes could mediate cell-cell communication in human cancerous development via transferring the various molecular cargos, including long non-coding RNA (lncRNA). Taurine up-regulated 1 (TUG1) was previously reported as an oncogenic lncRNA in cervical cancer (CC) via facilitating cell proliferation and other vital biological behaviors. Nevertheless, the presence of TUG1 in exosomes and the functional regulation of exosomal TUG1 in CC are still elusive. The current study aimed at the communication between CC cell lines and endothelial cell-mediated by exosomes, as well as the roles of exosomes derived from CC cells and exosomal TUG1 in affecting angiogenesis. Initially, it was found that TUG1 expression was upregulated in both CC cells and their secreted exosomes. TUG1 was transferred from CC cells to recipient human umbilical vein endothelial cells (HUVECs) in the exosomes way. Interestingly, TUG1 depletion impaired the exosomes-mediated proangiogenic potential of HUVECs by modulating certain key angiogenesis-related genes. In addition, exosomal TUG1 contributed to HUVECs proliferation through suppressing caspase-3 activity and impacting apoptosis-related proteins. Collectively, we identified a new exosomes-mediated molecular mechanism by which CC cells transferred TUG1 via exosomes to recipient HUVECs, thus promoting angiogenesis, providing a promising target for early diagnosis of CC.
越来越多的证据表明,外泌体可以通过传递各种分子货物(包括长链非编码 RNA [lncRNA])在人类癌症发展中介导细胞间通讯。先前有研究报道,牛磺酸上调基因 1(TUG1)可通过促进细胞增殖和其他重要的生物学行为,作为宫颈癌(CC)中的致癌 lncRNA。然而,TUG1 在外泌体中的存在以及外泌体 TUG1 在 CC 中的功能调节仍然难以捉摸。本研究旨在探讨 CC 细胞系与内皮细胞之间通过外泌体进行的通讯,以及源自 CC 细胞的外泌体和外泌体 TUG1 在影响血管生成中的作用。最初发现,TUG1 在 CC 细胞及其分泌的外泌体中均上调。TUG1 通过外泌体的方式从 CC 细胞转移到受体人脐静脉内皮细胞(HUVEC)。有趣的是,TUG1 耗竭通过调节某些关键的血管生成相关基因,损害了外泌体介导的 HUVEC 促血管生成潜能。此外,外泌体 TUG1 通过抑制 caspase-3 活性和影响凋亡相关蛋白,促进 HUVECs 的增殖。总之,我们确定了一种新的外泌体介导的分子机制,通过该机制,CC 细胞通过外泌体将 TUG1 转移到受体 HUVEC,从而促进血管生成,为 CC 的早期诊断提供了一个有前途的靶点。