TMPO-AS1/miR-98-5p/EBF1 feedback loop contributes to the progression of bladder cancer

Int J Biochem Cell Biol. 2020 May:122:105702. doi: 10.1016/j.biocel.2020.105702. Epub 2020 Feb 19.

Abstract

As reported in numerous studies, long non-coding RNAs (lncRNAs) exert significant effect on the regulation of tumor development. LncRNA TMPO antisense RNA 1 (TMPO-AS1) has been confirmed to be implicated in the development of several cancers. However, its clinical significance is still largely unknown in bladder cancer (BCa). In this study, high expression of TMPO-AS1 was revealed in BCa tissues and cell lines, and TMPO-AS1 predicted poor prognosis. Moreover, TMPO-AS1 facilitated cell growth. Additionally, TMPO-AS1 also boosted the migration and invasion of BCa cells. Mechanistically, overexpressed EBF transcription factor 1 (EBF1) in BCa cell was verified to promote the transcription of TMPO-AS1. Later, we found that TMPO-AS1 was a cytoplasmic RNA and could sponge miR-98-5p. Besides, it was validated that EBF1 is a target gene of miR-98-5p and negatively correlated with miR-98-5p in terms of expression level. According to the results of rescue experiments, we observed that EBF1 overexpression restored the repressive effect of TMPO-AS1 silencing on BCa development. Our research is the first to disclose the biological role and molecular mechanism of TMPO-AS1 in BCa, and TMPO-AS1 might be identified as a new therapeutic target for BCa patients.

Keywords: Bladder cancer; EBF1; TMPO-AS1; miR-98-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Growth Processes / physiology
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Disease Progression
  • Feedback, Physiological
  • Female
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Nuclear Proteins / genetics*
  • Prognosis
  • RNA, Antisense / biosynthesis
  • RNA, Antisense / metabolism*
  • Signal Transduction
  • Thymopoietins / genetics*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transfection
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology

Substances

  • EBF1 protein, human
  • MIRN98 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Antisense
  • Thymopoietins
  • Trans-Activators
  • TMPO protein, human