The lncRNA ELF3-AS1 promotes bladder cancer progression by interaction with Krüppel-like factor 8

Biochem Biophys Res Commun. 2019 Jan 15;508(3):762-768. doi: 10.1016/j.bbrc.2018.11.183. Epub 2018 Dec 7.

Abstract

Accumulating evidence has shown the critical role of long non-coding RNAs (lncRNAs) during cancer progression. However, the involvement of ELF3-AS1 in bladder cancer (BC) remains largely unclear. By lncRNA profiling, we identified ELF3-AS1 as a novel oncogenic lncRNA during bladder cancer development. ELF3-AS1 was highly expressed in bladder cancer and correlated with poor prognosis. ELF3-AS1 could increase viability and migration of bladder cancer cells in vitro and promoted xenograft tumor growth in vivo. Furthermore, ELF3-AS1 could interact with KLF8 to stabilize KLF8 by protecting it from proteasome-mediated degradation. KLF8 in turn could bind ELF3-AS1 promoter and transactivate ELF3-AS1 expression. The positive feedback loop between ELF3-AS1 and KLF8 enhanced KLF8 signaling by increasing MMP9 expression. Collectively, our study has unraveled a novel mechanism of ELF3-AS1-mediated oncogenesis in bladder cancer by reinforcement of ELF3-AS1/KLF8 signaling with potential implications for therapeutic intervention.

Keywords: Bladder cancer; ELF3-AS1; KLF8.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Progression*
  • Feedback, Physiological
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kruppel-Like Transcription Factors
  • Mice, Nude
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • Transcriptional Activation / genetics
  • Up-Regulation / genetics
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • KLF8 protein, human
  • Kruppel-Like Transcription Factors
  • RNA, Long Noncoding
  • Repressor Proteins