Exosomal taurine up-regulated 1 promotes angiogenesis and endothelial cell proliferation in cervical cancer

Cancer Biol Ther. 2020 Aug 2;21(8):717-725. doi: 10.1080/15384047.2020.1764318. Epub 2020 May 20.

Abstract

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.

Keywords: Exosomes; angiogenesis; cervical cancer; lncRNA TUG1; proliferation.

MeSH terms

  • Cell Proliferation
  • Endothelial Cells / metabolism*
  • Exosomes / metabolism*
  • Female
  • Humans
  • RNA, Long Noncoding / metabolism*
  • Transfection
  • Uterine Cervical Neoplasms / genetics*

Substances

  • RNA, Long Noncoding
  • TUG1 long noncoding RNA, human