Circ-ITCH regulates triple-negative breast cancer progression through the Wnt/β-catenin pathway

Neoplasma. 2019 Mar 5;66(2):232-239. doi: 10.4149/neo_2018_180710N460. Epub 2018 Sep 29.

Abstract

Recent studies indicate that circular RNA (circRNA) is involved in tumorigenesis, but its role in triple-negative breast cancer (TNBC) remains largely unknown. In this study, we characterized the role of circ-ITCH in TNBC and found that circ-ITCH was significantly down-regulated in TNBC tissues and cell lines and closely associated with poor prognosis. We therefore constructed the MDA-MB-231 and BT-549 TNBC cell lines stably expressing circ-ITCH by lentiviral vectors to determine its underlying mechanisms in TNBC progression. Most importantly, over-expression of circ-ITCH remarkably inhibited TNBC proliferation, invasion and metastasis both in vitro and in vivo. Mechanistically, we found that circ-ITCH acts as a sponge for miR-214 and miR-17 to increase expression of its ITCH linear isoform, thereby inactivating Wnt/β-catenin signaling. Our combined results show for the first time that circ-ITCH is a tumor suppressor, a promising prognostic biomarker in TNBC and that its restoration could well be a successful strategy in TNBC.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Humans
  • MicroRNAs / genetics
  • RNA / genetics*
  • RNA, Circular
  • Repressor Proteins / genetics*
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology
  • Ubiquitin-Protein Ligases / genetics*
  • Wnt Signaling Pathway*

Substances

  • MIRN17 microRNA, human
  • MIRN214 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Repressor Proteins
  • RNA
  • ITCH protein, human
  • Ubiquitin-Protein Ligases