Double-negative feedback loop between long non-coding RNA TUG1 and miR-145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells

FEBS Lett. 2015 Oct 7;589(20 Pt B):3175-81. doi: 10.1016/j.febslet.2015.08.020. Epub 2015 Aug 28.


LncRNAs have a critical role in the regulation of cellular processes such as cancer progression and metastasis. In the present study, we confirmed that TUG1 was overexpressed in bladder cancer tissues and established cell lines. Knockdown of TUG1 inhibited bladder cancer cell metastasis both in vitro and in vivo. Furthermore, we found that TUG1 promoted cancer cell invasion and radioresistance through inducing epithelial-to-mesenchymal transition (EMT). Interestingly, TUG1 decreased the expression of miR-145 and there was a reciprocal repression between TUG1 and miR-145 in an Argonaute2-dependent manner. ZEB2 was identified as a down-stream target of miR-145 and TUG1 exerted its function through the miR-145/ZEB2 axis. In summary, our data indicated that blocking TUG1 function may be an effective anti-cancer therapy.

Keywords: Bladder cancer; Epithelial-to-mesenchymal transition; Radioresistance; TUG1; ZEB2; miR-145.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / genetics*
  • Feedback, Physiological
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HEK293 Cells
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Radiation Tolerance / genetics
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Transplantation, Heterologous
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology
  • Zinc Finger E-box Binding Homeobox 2


  • 3' Untranslated Regions
  • Homeodomain Proteins
  • MIRN145 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Repressor Proteins
  • TUG1 long noncoding RNA, human
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2