LncRNA EGOT decreases breast cancer cell viability and migration via inactivation of the Hedgehog pathway

FEBS Open Bio. 2020 May;10(5):817-826. doi: 10.1002/2211-5463.12833. Epub 2020 Apr 8.

Abstract

The long noncoding RNA (lncRNA) Eosinophil Granule Ontogeny Transcript (EGOT) has been reported to inhibit the proliferation and migration of glioma cells, and promote the development and progression of gastric cancer through the Hedgehog (Hh) signaling pathway. This study was conducted to assess the role of EGOT in the progression of breast cancer. We observed that EGOT is significantly down-regulated in breast cancer tissues and cell lines, and EGOT expression is negatively correlated with the Ki67 expression. Overexpression of EGOT in BT549 cells decreased cell viability and migration. In addition, overexpression of EGOT resulted in decreases in expression of key genes in the Hh pathway, including Gli1, smoothened protein, protein patched homolog 1 and Hedgehog-interacting protein (HHIP). Breast cancer tissues exhibited an increase in Gli1 expressions. Altered expression of Gli1, smoothened protein, protein patched homolog 1 and HHIP caused by EGOT overexpression were fully restored in cells transfected with plasmid complementory DNA (pcDNA) EGOT and treated with purmorphamine, an agonist of the Hh pathway. Cell viability and migration were also restored by purmorphamine. We conclude that lncRNA EGOT may inhibit breast cancer cell viability and migration via inactivation of the Hh pathway.

Keywords: Hedgehog pathway; breast cancer; cell migration; cell proliferation; lncRNA EGOT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • China
  • Female
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Hedgehog Proteins / metabolism*
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Patched-1 Receptor / genetics
  • Patched-1 Receptor / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Signal Transduction / genetics
  • Zinc Finger Protein GLI1 / genetics
  • Zinc Finger Protein GLI1 / metabolism

Substances

  • Carrier Proteins
  • EGOT lncRNA, human
  • HHIP protein, human
  • Hedgehog Proteins
  • Membrane Glycoproteins
  • PTCH1 protein, human
  • Patched-1 Receptor
  • RNA, Long Noncoding
  • Zinc Finger Protein GLI1