Knockdown of long non-coding RNA TUG1 suppresses nasopharyngeal carcinoma progression by inhibiting epithelial-mesenchymal transition (EMT) via the promotion of miR-384

Biochem Biophys Res Commun. 2019 Jan 29;509(1):56-63. doi: 10.1016/j.bbrc.2018.12.011. Epub 2018 Dec 21.

Abstract

Nasopharyngeal carcinoma (NPC) is a cancer arising from the nasopharynx epithelium. Long non-coding RNAs (lnc RNA) play a critical role in various biological processes such as cell growth, embryonic development, and tumorigenesis. In the study, for the first time, we discovered that lnc RNA taurine upregulated gene 1 (TUG1) exhibited higher expression levels in NPC tissues and NPC cell lines than in normal nasopharyngeal epithelial tissues and normal nasopharyngeal cell line. In addition, patients with NPCs showing higher levels of TUG1 had worse overall survivals. Further, suppressing TUG1 expression markedly reduced the cell proliferation, migration and invasion; however, TUG1 over-expression significantly enhanced the proliferation, migration and invasion in NPC cells. TUG1 knockdown-inhibited epithelial-mesenchymal transition (EMT) was evidenced by the reduced expression of Vimentin, N-cadherin and transforming growth factor (TGF)-β1, while the enhanced level of E-cadherin. The results of luciferase reporter analysis verified that miR-384 was a direct target of TUG1 in NPC, and was down-regulated in NPC tissues, exhibiting suppressive role in cell proliferation, migration and invasion. In vivo, TUG1 knockdown reduced tumor growth via the regulation of miR-384 by restraining EMT development. In conclusion, our findings suggested that there was a negative correlation between TUG1 and miR-384 in NPC patients. TUG1 might be an effective candidate for use in NPC diagnosis, prognosis and treatment.

Keywords: EMT; Lnc RNA TUG1; Migration and invasion; Nasopharyngeal carcinoma (NPC); miR-384.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Progression
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Nasopharyngeal Carcinoma / genetics*
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • RNA, Long Noncoding / genetics*

Substances

  • MIRN384 microRNA, human
  • MIRN384 microRNA, mouse
  • MicroRNAs
  • RNA, Long Noncoding
  • TUG1 long noncoding RNA, human